40665-68-7

Basic information

• Product Name: DIMETHYL(3-PHENOXY-2-OXOPROPYL)PHOSPHONATE
• Synonyms: Dimethyl(2-oxo-3-phenoxypropyl)phosphonate;Dimethyl[(3-phenoxyacetyl)methyl]phosphonate;(2-OXO-3-PHENOXY-PROPYL)-PHOSPHONIC ACID DIMETHYL ESTER;DIMETHYL)2-OXO-3-PHENOXPROPYL)PHOSPHONATE;Dimethyl(3-phenoxy-2-oxopropyl)phosphonate, min. 90 %;(3-Phenoxy-2-oxopropyl)phosphonic acid dimethyl ester;(3-Phenoxyacetonyl)phosphonic acid dimethyl ester;[2-Oxo-3phenoxy-propyl]-phosphonic
• CAS NO: 40665-68-7
• Molecular Formula: C₁₁H₁₅O₅P
• Molecular Weight: 258.21
• Mol File: 40665-68-7.mol
• Article Data: 17

Chemical Properties

• Boiling Point: 175°C/0.5mmHg(lit.)
• Flash Point: 191.1 °C
• Appearance: /
• Density: 1.21 g/cm³
• Vapor Pressure: 1.16E-05mmHg at 25°C
• Refractive Index: 1.5150-1.5190
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• CAS DataBase Reference: DIMETHYL(3-PHENOXY-2-OXOPROPYL)PHOSPHONATE(CAS DataBase Reference)
• NIST Chemistry Reference: DIMETHYL(3-PHENOXY-2-OXOPROPYL)PHOSPHONATE(40665-68-7)
• EPA Substance Registry System: DIMETHYL(3-PHENOXY-2-OXOPROPYL)PHOSPHONATE(40665-68-7)

Safety Data

• Statements: 36/37/38
• Safety Statements: 26-36/37/39
• Hazardous Substances Data: 40665-68-7(Hazardous Substances Data)

Usage

Description

DIMETHYL(3-PHENOXY-2-OXOPROPYL)PHOSPHONATE, also known as Travopropst (T715600), is a compound that acts as a selective FP prostaglandin receptor agonist. It is the isopropyl ester of (+)-fluprostenol, a prostaglandin analog, and is characterized by its ability to interact with specific receptors in the body, playing a role in various physiological processes.

Uses

Used in Pharmaceutical Industry:
DIMETHYL(3-PHENOXY-2-OXOPROPYL)PHOSPHONATE is used as an active pharmaceutical ingredient for its antiglaucoma properties. It helps in the treatment of glaucoma by reducing intraocular pressure, which is a primary risk factor for vision loss in patients with this condition.
Used in Research and Development:
DIMETHYL(3-PHENOXY-2-OXOPROPYL)PHOSPHONATE is used as a key compound in the synthesis of novel prostanoid thromboxane A2 agonists. These agonists have potential applications in various medical fields, including the treatment of cardiovascular and respiratory diseases, as well as other conditions that involve the prostanoid system.

InChI:InChI=1/C11H15O5P/c1-14-17(13,15-2)9-10(12)8-16-11-6-4-3-5-7-11/h3-7H,8-9H2,1-2H3

Synthetic route

methyl 2-phenoxyacetate (2065-23-8) + dimethyl methane phosphonate (756-79-6) → dimethyl (3-phenoxy-2-oxopropyl)phosphonate (40665-68-7)

Conditions	Yield
Stage #1: dimethyl methane phosphonate With n-butyllithium In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere; Stage #2: methyl 2-phenoxyacetate In tetrahydrofuran at -78 - 20℃; for 2.5h; Inert atmosphere;	83%
Stage #1: dimethyl methane phosphonate With n-butyllithium In tetrahydrofuran at -78℃; Inert atmosphere; Stage #2: methyl 2-phenoxyacetate In tetrahydrofuran at 25℃;	25%
With n-butyllithium 1.) THF, hexane, -78 deg C, 5 min, 2.) -78 deg C, 2 h; Yield given. Multistep reaction;
With n-butyllithium In tetrahydrofuran; hexane; water

methyl 2-phenoxyacetate (2065-23-8) + dimethyl lithiomethylphosphonate (34939-91-8, 58648-56-9) → dimethyl (3-phenoxy-2-oxopropyl)phosphonate (40665-68-7)

Conditions	Yield
In tetrahydrofuran at -78℃;

bis-tetrahydropyran-2-yl ether (709-84-2) + n-butyllithium (109-72-8, 29786-93-4) + Phenoxyacetyl chloride (701-99-5) + dimethyl methane phosphonate (756-79-6) → dimethyl (3-phenoxy-2-oxopropyl)phosphonate (40665-68-7)

Conditions	Yield
In tetrahydrofuran; hexane; water

phenoxyacetic acid ethyl ester (2555-49-9) + dimethyl methane phosphonate (756-79-6) → dimethyl (3-phenoxy-2-oxopropyl)phosphonate (40665-68-7)

Conditions	Yield
With n-butyllithium In tetrahydrofuran; hexane
With n-butyllithium In tetrahydrofuran; hexane

Phenoxyacetyl chloride (701-99-5) + dimethyl methane phosphonate (756-79-6) → dimethyl (3-phenoxy-2-oxopropyl)phosphonate (40665-68-7)

Conditions	Yield
In tetrahydrofuran; hexane
In tetrahydrofuran; hexane

methyl 9α-acetoxy-11α-(2-tetrahydropyranyloxy)-15α-hdroxy-16-phenoxy-17,18,19,20-tetranorprosta-cis-5,trans-13-dienoate + phenoxyacetic acid ethyl ester (2555-49-9) + dimethyl methane phosphonate (756-79-6) → dimethyl (3-phenoxy-2-oxopropyl)phosphonate (40665-68-7)

Conditions	Yield
With n-butyllithium In tetrahydrofuran; hexane

phenol (108-95-2) → dimethyl (3-phenoxy-2-oxopropyl)phosphonate (40665-68-7)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: potassium carbonate / acetone / 16 h / 25 - 56 °C 2.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 2.2: 2.5 h / -78 - 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1.1: sodium hydroxide / water / 0.67 h / 25 °C 1.2: 16 h / 30 - 35 °C 2.1: zinc(II) chloride / toluene / 6 h / 65 - 70 °C / Inert atmosphere 3.1: Jones reagent / acetone / 7 h / Cooling with ice View Scheme

Phenyl glycidyl ether (122-60-1) → dimethyl (3-phenoxy-2-oxopropyl)phosphonate (40665-68-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: zinc(II) chloride / toluene / 6 h / 65 - 70 °C / Inert atmosphere 2: Jones reagent / acetone / 7 h / Cooling with ice View Scheme

2-hydroxy-3-phenoxypropyldimethylphosphonate → dimethyl (3-phenoxy-2-oxopropyl)phosphonate (40665-68-7)

Conditions	Yield
With Jones reagent In acetone for 7h; Cooling with ice;	92.8 g

dimethyl (3-phenoxy-2-oxopropyl)phosphonate (40665-68-7) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (3aR,4R,5R,6aS)-2-oxo-4-((E)-3-oxo-4-phenoxybut-1-en-1-yl)hexahydro-2H-cyclopenta[b]furan-5-yl benzoate (51638-91-6)

Conditions	Yield
With sodium hydride Horner-Emmons reaction;	90%
Stage #1: dimethyl (3-phenoxy-2-oxopropyl)phosphonate With sodium hydride; zinc(II) chloride In tetrahydrofuran; mineral oil at 25 - 35℃; for 0.416667h; Inert atmosphere; Stage #2: (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one In tetrahydrofuran; dichloromethane; mineral oil at 25 - 40℃; for 2.08333h; Inert atmosphere;	61%
Stage #1: dimethyl (3-phenoxy-2-oxopropyl)phosphonate With sodium hydroxide; zinc(II) chloride In tetrahydrofuran at 27℃; Inert atmosphere; Stage #2: (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one In tetrahydrofuran at 27℃; for 15h; Inert atmosphere;	50%

dimethyl (3-phenoxy-2-oxopropyl)phosphonate (40665-68-7) + isopropyl (Z)-7-((1R,2R,3R,5S)-5-acetoxy-2-formyl-3-((tetrahydro-2H-pyran-2-yl)oxy)cyclopentyl)hept-5-enoate → isopropyl (Z)-7-((1R,2R,3R,5S)-5-acetoxy-2-((E)-3-oxo-4-phenoxybut-1-en-1-yl)-3-((tetrahydro-2H-pyran-2-yl)oxy)cyclopentyl)hept-5-enoate

Conditions

Yield

Stage #1: dimethyl (3-phenoxy-2-oxopropyl)phosphonate With n-butyllithium; tetrabutylammomium bromide In dichloromethane at 20 - 30℃; for 1h; Horner-Wadsworth-Emmons Olefination; Stage #2: isopropyl (Z)-7-((1R,2R,3R,5S)-5-acetoxy-2-formyl-3-((tetrahydro-2H-pyran-2-yl)oxy)cyclopentyl)hept-5-enoate In dichloromethane at 20℃; for 15h; Reagent/catalyst; Solvent; Temperature; Horner-Wadsworth-Emmons Olefination;

85.4%

dimethyl (3-phenoxy-2-oxopropyl)phosphonate (40665-68-7) + 2α-(6-methoxycarbonylhexyl)-3β-formyloxycyclopent-1-one (38698-56-5, 61659-10-7, 62769-46-4) → methyl 9,15-dioxo-16-phenoxy-13-trans-17,18,19,20-tetranorprostenoate (122437-70-1, 129444-27-5)

Conditions	Yield
With potassium hydroxide In dichloromethane for 1h; Ambient temperature;	68%

dimethyl (3-phenoxy-2-oxopropyl)phosphonate (40665-68-7) + (Z)-4-formyl-5-(7-isopropoxy-7-oxohept-2-enyl)cyclopentane-1,3-diyl dibenzoate → 4-((Z)-7-isopropoxy-7-oxohept-2-enyl)-5-((E)-3-oxo-4-phenoxybut-1-enyl)cyclopentane-1,3-diyl dibenzoate

Conditions	Yield
Stage #1: dimethyl (3-phenoxy-2-oxopropyl)phosphonate With sodium hydride In 1,2-dimethoxyethane at -5 - 25℃; for 1.25h; Horner-Wadsworth-Emmons olefination; Inert atmosphere; Stage #2: (Z)-4-formyl-5-(7-isopropoxy-7-oxohept-2-enyl)cyclopentane-1,3-diyl dibenzoate In 1,2-dimethoxyethane at -5 - 25℃; for 2h; Horner-Wadsworth-Emmons olefination; Inert atmosphere;	60%

dimethyl (3-phenoxy-2-oxopropyl)phosphonate (40665-68-7) + C21H29NO6S → isopropyl 2-[(2R,4aR,5R,6R,7aS)-5-[(1E)-3-oxo-4-phenoxy-1-buten-1-yl]-6-(tetrahydro-2H-pyran-2-yloxy)octahydrocyclopenta[b]pyran-2-yl]-1,3-thiazole-4-carboxylate

Conditions	Yield
With triethylamine; lithium chloride In tetrahydrofuran at 20℃; for 16h;	52%

dimethyl (3-phenoxy-2-oxopropyl)phosphonate (40665-68-7) + 11-((1S,2R)-2-Formyl-5-oxo-cyclopentyl)-undecanoic acid methyl ester (129367-74-4) → 11-[(1S,5S)-2-Oxo-5-((E)-3-oxo-4-phenoxy-but-1-enyl)-cyclopentyl]-undecanoic acid methyl ester (129367-85-7)

Conditions	Yield
With potassium hydroxide In dichloromethane for 1h; Ambient temperature;	50%

dimethyl (3-phenoxy-2-oxopropyl)phosphonate (40665-68-7) + Biphenyl-4-carboxylic acid (3aS,5S,6aR)-4-formyl-2-oxo-octahydro-cyclopenta[b]pyrrol-5-yl ester (78845-62-2, 111900-95-9) → Biphenyl-4-carboxylic acid (3aS,5S,6aR)-2-oxo-4-((E)-3-oxo-4-phenoxy-but-1-enyl)-octahydro-cyclopenta[b]pyrrol-5-yl ester (111803-58-8)

Conditions	Yield
With sodium hydride In 1,2-dimethoxyethane Ambient temperature; 1.) 0.5 h 2.) 3 h;	19%

dimethyl (3-phenoxy-2-oxopropyl)phosphonate (40665-68-7) + Corey aldehyde (62961-72-2) → 7α-hydroxy-6β-(3'-oxo-4'-phenoxy-1'E-butenyl)-2-oxabicyclo<3.3.0>octan-3-one (871669-32-8)

Conditions	Yield
With potassium carbonate at 20℃; for 5h; Yield given;

dimethyl (3-phenoxy-2-oxopropyl)phosphonate (40665-68-7) + 7α-trimethylsilyloxy-6β-formyl-2-oxabicyclo<3.3.0>octan-3-one (122517-79-7) → 7α-trimethylsilyloxy-6β-(3'-oxo-4'-phenoxy-1'E-butenyl)-2-oxabicyclo<3.3.0>octan-3-one (871669-30-6)

Conditions	Yield
With potassium hydroxide In dichloromethane for 0.333333h; Ambient temperature; Yield given;

dimethyl (3-phenoxy-2-oxopropyl)phosphonate (40665-68-7) + methyl <1α,2α(Z),3α,4α>-7-<3-formyl-7-oxabicyclo<2.2.1>hept-2-yl>-5-heptenoate (104596-33-0) → (Z)-7-[(1S,2R,3S,4R)-3-((E)-3-Oxo-4-phenoxy-but-1-enyl)-7-oxa-bicyclo[2.2.1]hept-2-yl]-hept-5-enoic acid methyl ester (87929-54-2)

Conditions	Yield
With sodium hydride 1.) DME, 2.) 23 deg C; Multistep reaction;

dimethyl (3-phenoxy-2-oxopropyl)phosphonate (40665-68-7) + 2α-(7-methoxycarbonyl-4Z-heptenyl)-3β-formylcyclopentanone (88736-15-6) → methyl 1-homo-3,4-cis-didehydro-9,15-diketo-16-phenoxy-17,18,19,20-tetranorprostenoate (131846-19-0)

Conditions	Yield
With sodium hydride 1.) THF, RT, 1.5 h, 2.) THF, RT, 30 min; Yield given. Multistep reaction;

dimethyl (3-phenoxy-2-oxopropyl)phosphonate (40665-68-7) + 7-(4-Formyl-furan-3-yl)-heptanoic acid methyl ester (78932-40-8) → 7-[4-((E)-3-Oxo-4-phenoxy-but-1-enyl)-furan-3-yl]-heptanoic acid methyl ester

dimethyl (3-phenoxy-2-oxopropyl)phosphonate (40665-68-7) + methyl (Z)-7-[(1R,2R,3R,5S)-5-acetoxy-2-formyl-3-(2-tetrahydropyranyloxy)cyclopentyl]-5-heptenate (61218-06-2) → 16-phenoxy-17,18,19,20-tetranor-15-dehydroprostaglandin F2α 9-acetate methyl ester 11-(tetrahydropyran-2-yl ether) (62561-47-1)

Conditions	Yield
With sodium hydride 1.) THF, 25 deg C, 20 min, 2.) THF, from 25 deg C to 60 deg C, 4.5 h; Yield given. Multistep reaction;

dimethyl (3-phenoxy-2-oxopropyl)phosphonate (40665-68-7) + C64H110O17Si3 (141242-63-9) → C73H118O18Si3 (141242-73-1)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; lithium chloride In acetonitrile Ambient temperature; Yield given;

dimethyl (3-phenoxy-2-oxopropyl)phosphonate (40665-68-7) + (3aR,4R,5R,6aS)-4-formyl-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl biphenyl-4-carboxylate (38754-71-1) → Biphenyl-4-carboxylic acid (3aR,4R,5R,6aS)-2-oxo-4-((E)-3-oxo-4-phenoxy-but-1-enyl)-hexahydro-cyclopenta[b]furan-5-yl ester (79171-99-6)

Conditions	Yield
With sodium hydride 1.) THF, 90 min, 2.) THF, 30 min; Yield given. Multistep reaction;
Stage #1: dimethyl (3-phenoxy-2-oxopropyl)phosphonate; (3aR,4R,5R,6aS)-4-formyl-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl biphenyl-4-carboxylate With water; lithium hydroxide In dichloromethane at 5 - 22℃; for 19.5h; Stage #2: With citric acid In dichloromethane at 22℃; pH=1-2; Reagent/catalyst;	8.7 g

dimethyl (3-phenoxy-2-oxopropyl)phosphonate (40665-68-7) → 7α-hydroxy-6β-(3'-hydroxy-4'-phenoxy-1'E-butenyl)-2-oxabicyclo<3.3.0>octan-3-one (51638-93-8, 60761-96-8, 63324-34-5, 103616-92-8, 127760-07-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: K2CO3 / 5 h / 20 °C 2: 90 percent / aluminum diisobutyl-4-methyl-2,6-di-tert-butylphenoxide / CH2Cl2 / 0.5 h / -78 °C View Scheme
Multi-step reaction with 3 steps 1: KOH / CH2Cl2 / 0.33 h / Ambient temperature 2: 1 N hydrochloric acid / acetone / 0.17 h / 20 °C 3: 90 percent / aluminum diisobutyl-4-methyl-2,6-di-tert-butylphenoxide / CH2Cl2 / 0.5 h / -78 °C View Scheme

dimethyl (3-phenoxy-2-oxopropyl)phosphonate (40665-68-7) → 7α-hydroxy-6β-(3'-oxo-4'-phenoxy-1'E-butenyl)-2-oxabicyclo<3.3.0>octan-3-one (871669-32-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: KOH / CH2Cl2 / 0.33 h / Ambient temperature 2: 1 N hydrochloric acid / acetone / 0.17 h / 20 °C View Scheme

dimethyl (3-phenoxy-2-oxopropyl)phosphonate (40665-68-7) → 7α-trimethylsilyloxy-6β-(3'α-trimethylsilyloxy-4'-phenoxy-1'E-butenyl)-2-oxabicyclo<3.3.0>octan-3-ol (127718-28-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: K2CO3 / 5 h / 20 °C 2: 90 percent / aluminum diisobutyl-4-methyl-2,6-di-tert-butylphenoxide / CH2Cl2 / 0.5 h / -78 °C 3: 85 percent / pyridine / 2 h / 5 °C 4: 0.24 g / i-Bu2AlH / CH2Cl2 / 1 h / -78 °C View Scheme
Multi-step reaction with 5 steps 1: KOH / CH2Cl2 / 0.33 h / Ambient temperature 2: 1 N hydrochloric acid / acetone / 0.17 h / 20 °C 3: 90 percent / aluminum diisobutyl-4-methyl-2,6-di-tert-butylphenoxide / CH2Cl2 / 0.5 h / -78 °C 4: 85 percent / pyridine / 2 h / 5 °C 5: 0.24 g / i-Bu2AlH / CH2Cl2 / 1 h / -78 °C View Scheme

dimethyl (3-phenoxy-2-oxopropyl)phosphonate (40665-68-7) → 7α-trimethylsilyloxy-6β-(3'α-trimethylsilyloxy-4'-phenoxy-1'E-butenyl)-2-oxabicyclo<3.3.0>octan-3-one (127702-12-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: K2CO3 / 5 h / 20 °C 2: 90 percent / aluminum diisobutyl-4-methyl-2,6-di-tert-butylphenoxide / CH2Cl2 / 0.5 h / -78 °C 3: 85 percent / pyridine / 2 h / 5 °C View Scheme
Multi-step reaction with 4 steps 1: KOH / CH2Cl2 / 0.33 h / Ambient temperature 2: 1 N hydrochloric acid / acetone / 0.17 h / 20 °C 3: 90 percent / aluminum diisobutyl-4-methyl-2,6-di-tert-butylphenoxide / CH2Cl2 / 0.5 h / -78 °C 4: 85 percent / pyridine / 2 h / 5 °C View Scheme

dimethyl (3-phenoxy-2-oxopropyl)phosphonate (40665-68-7) → N-(methanesulfonyl)-16-phenox-ω-tetranor-PGF2α-carboxamide (79172-00-2)

Conditions	Yield
Multi-step reaction with 5 steps 1: K2CO3 / 5 h / 20 °C 2: 90 percent / aluminum diisobutyl-4-methyl-2,6-di-tert-butylphenoxide / CH2Cl2 / 0.5 h / -78 °C 3: 85 percent / pyridine / 2 h / 5 °C 4: 0.24 g / i-Bu2AlH / CH2Cl2 / 1 h / -78 °C 5: 2.) 1 N hydrochloric acid / 1.) benzene, 20 deg C, 3 h, 2.) 10 min View Scheme
Multi-step reaction with 6 steps 1: KOH / CH2Cl2 / 0.33 h / Ambient temperature 2: 1 N hydrochloric acid / acetone / 0.17 h / 20 °C 3: 90 percent / aluminum diisobutyl-4-methyl-2,6-di-tert-butylphenoxide / CH2Cl2 / 0.5 h / -78 °C 4: 85 percent / pyridine / 2 h / 5 °C 5: 0.24 g / i-Bu2AlH / CH2Cl2 / 1 h / -78 °C 6: 2.) 1 N hydrochloric acid / 1.) benzene, 20 deg C, 3 h, 2.) 10 min View Scheme
Multi-step reaction with 7 steps 1: 1.) NaH / 1.) THF, 90 min, 2.) THF, 30 min 2: 25 percent / lithium triethylborohydride / tetrahydrofuran / 0.5 h 3: potassium carbonate / methanol; tetrahydrofuran / 2.5 h 4: 95 percent / p-toluenesulfonic acid / CH2Cl2 / 0.5 h 5: 79 percent / diisobutylaluminum hydride / toluene; hexane / 0.33 h 6: 1.) sodium methylsulfinylcarbanide / 1.) Me2SO, 2.) Me2SO, 2 h 7: 40 percent / 65percent aq. acetic acid / 14 h View Scheme

dimethyl (3-phenoxy-2-oxopropyl)phosphonate (40665-68-7) → N-{(Z)-7-[(1R,2R,3R)-5-Oxo-2-((E)-(R)-4-phenoxy-3-trimethylsilanyloxy-but-1-enyl)-3-trimethylsilanyloxy-cyclopentyl]-hept-5-enoyl}-methanesulfonamide

Conditions	Yield
Multi-step reaction with 7 steps 1: K2CO3 / 5 h / 20 °C 2: 90 percent / aluminum diisobutyl-4-methyl-2,6-di-tert-butylphenoxide / CH2Cl2 / 0.5 h / -78 °C 3: 85 percent / pyridine / 2 h / 5 °C 4: 0.24 g / i-Bu2AlH / CH2Cl2 / 1 h / -78 °C 5: 2.) 1 N hydrochloric acid / 1.) benzene, 20 deg C, 3 h, 2.) 10 min 6: 90 percent / acetone / 1.5 h / -45 °C 7: CrO3/pyridine / CH2Cl2 View Scheme
Multi-step reaction with 8 steps 1: KOH / CH2Cl2 / 0.33 h / Ambient temperature 2: 1 N hydrochloric acid / acetone / 0.17 h / 20 °C 3: 90 percent / aluminum diisobutyl-4-methyl-2,6-di-tert-butylphenoxide / CH2Cl2 / 0.5 h / -78 °C 4: 85 percent / pyridine / 2 h / 5 °C 5: 0.24 g / i-Bu2AlH / CH2Cl2 / 1 h / -78 °C 6: 2.) 1 N hydrochloric acid / 1.) benzene, 20 deg C, 3 h, 2.) 10 min 7: 90 percent / acetone / 1.5 h / -45 °C 8: CrO3/pyridine / CH2Cl2 View Scheme

dimethyl (3-phenoxy-2-oxopropyl)phosphonate (40665-68-7) → N-{(Z)-7-[(1R,2R,3R,5S)-5-Hydroxy-2-((E)-(R)-4-phenoxy-3-trimethylsilanyloxy-but-1-enyl)-3-trimethylsilanyloxy-cyclopentyl]-hept-5-enoyl}-methanesulfonamide (127718-29-0)

Conditions	Yield
Multi-step reaction with 6 steps 1: K2CO3 / 5 h / 20 °C 2: 90 percent / aluminum diisobutyl-4-methyl-2,6-di-tert-butylphenoxide / CH2Cl2 / 0.5 h / -78 °C 3: 85 percent / pyridine / 2 h / 5 °C 4: 0.24 g / i-Bu2AlH / CH2Cl2 / 1 h / -78 °C 5: 2.) 1 N hydrochloric acid / 1.) benzene, 20 deg C, 3 h, 2.) 10 min 6: 90 percent / acetone / 1.5 h / -45 °C View Scheme
Multi-step reaction with 7 steps 1: KOH / CH2Cl2 / 0.33 h / Ambient temperature 2: 1 N hydrochloric acid / acetone / 0.17 h / 20 °C 3: 90 percent / aluminum diisobutyl-4-methyl-2,6-di-tert-butylphenoxide / CH2Cl2 / 0.5 h / -78 °C 4: 85 percent / pyridine / 2 h / 5 °C 5: 0.24 g / i-Bu2AlH / CH2Cl2 / 1 h / -78 °C 6: 2.) 1 N hydrochloric acid / 1.) benzene, 20 deg C, 3 h, 2.) 10 min 7: 90 percent / acetone / 1.5 h / -45 °C View Scheme

dimethyl (3-phenoxy-2-oxopropyl)phosphonate (40665-68-7) → (3aR,4R,5R,6aS)-4-((E)-3,3-difluoro-4-phenoxybut-1-en-1-yl)-5-hydroxyhexahydro-2H-cyclopenta[b]furan-2-one (209861-01-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: NaH 2: morpholinosulfur trifluoride / CHCl3 / 82 h / 30 - 40 °C 3: K2CO3 / methanol / 3 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1: 90 percent / NaH 2: morpholinosulfur trifluoride / CHCl3 / 82 h / 30 - 40 °C 3: K2CO3 / methanol / 3 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1: lithium hydroxide monohydrate / tetrahydrofuran; water / 1 h / 20 °C 2: diethylamino-sulfur trifluoride / dichloromethane / 72 h / 20 °C 3: potassium carbonate / methanol / 1.5 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: lithium hydroxide; water / dichloromethane / 19.5 h / 5 - 22 °C 1.2: 22 °C / pH 1-2 2.1: diethylamino-sulfur trifluoride / dichloromethane / 94 h / 5 - 30 °C / Inert atmosphere 3.1: potassium carbonate / methanol / 2 h / 20 °C 3.2: 1 h / 0 °C / Acidic conditions View Scheme

dimethyl (3-phenoxy-2-oxopropyl)phosphonate (40665-68-7) → (3aR,4R,5R,6aS)-4-((E)-3,3-difluoro-4-phenoxybut-1-en-1-yl)hexahydro-2H-cyclopenta[b]furan-2,5-diol (209861-02-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: NaH 2: morpholinosulfur trifluoride / CHCl3 / 82 h / 30 - 40 °C 3: K2CO3 / methanol / 3 h / 20 °C 4: 83 percent / diisobutylaluminum hydride / tetrahydrofuran; toluene / 1 h / -78 °C View Scheme
Multi-step reaction with 4 steps 1: 90 percent / NaH 2: morpholinosulfur trifluoride / CHCl3 / 82 h / 30 - 40 °C 3: K2CO3 / methanol / 3 h / 20 °C 4: 83 percent / diisobutylaluminum hydride / tetrahydrofuran; toluene / 1 h / -78 °C View Scheme
Multi-step reaction with 3 steps 1.1: sodium hydride; zinc(II) chloride / mineral oil; tetrahydrofuran / 0.42 h / 25 - 35 °C / Inert atmosphere 1.2: 2.08 h / 25 - 40 °C / Inert atmosphere 2.1: diethylamino-sulfur trifluoride / dichloromethane / 24 h / 0 - 35 °C / Inert atmosphere 3.1: diisobutylaluminium hydride / toluene / 3.25 h / -65 - -61 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1: lithium hydroxide monohydrate / tetrahydrofuran; water / 1 h / 20 °C 2: diethylamino-sulfur trifluoride / dichloromethane / 72 h / 20 °C 3: potassium carbonate / methanol / 1.5 h / 20 °C 4: diisobutylaluminium hydride / tetrahydrofuran; hexane / 0.5 h / -70 °C View Scheme

dimethyl (3-phenoxy-2-oxopropyl)phosphonate (40665-68-7) → (3aR,4R,5R,6aS)-4-((E)-3,3-difluoro-4-phenoxybutan-1-en-1-yl)-hexahydro-2-oxo-2H-cyclopenta[b]furan-5-yl benzoate (209861-00-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: NaH 2: morpholinosulfur trifluoride / CHCl3 / 82 h / 30 - 40 °C View Scheme
Multi-step reaction with 2 steps 1: 90 percent / NaH 2: morpholinosulfur trifluoride / CHCl3 / 82 h / 30 - 40 °C View Scheme
Multi-step reaction with 2 steps 1.1: sodium hydride; zinc(II) chloride / mineral oil; tetrahydrofuran / 0.42 h / 25 - 35 °C / Inert atmosphere 1.2: 2.08 h / 25 - 40 °C / Inert atmosphere 2.1: diethylamino-sulfur trifluoride / dichloromethane / 24 h / 0 - 35 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: lithium hydroxide monohydrate / tetrahydrofuran; water / 1 h / 20 °C 2: diethylamino-sulfur trifluoride / dichloromethane / 72 h / 20 °C View Scheme

dimethyl (3-phenoxy-2-oxopropyl)phosphonate (40665-68-7) → AFP-172 (209860-88-8)

Conditions	Yield
Multi-step reaction with 5 steps 1: NaH 2: morpholinosulfur trifluoride / CHCl3 / 82 h / 30 - 40 °C 3: K2CO3 / methanol / 3 h / 20 °C 4: 83 percent / diisobutylaluminum hydride / tetrahydrofuran; toluene / 1 h / -78 °C 5: NaN(SiMe3)2 / tetrahydrofuran / 3 h / 0 °C View Scheme
Multi-step reaction with 5 steps 1: 90 percent / NaH 2: morpholinosulfur trifluoride / CHCl3 / 82 h / 30 - 40 °C 3: K2CO3 / methanol / 3 h / 20 °C 4: 83 percent / diisobutylaluminum hydride / tetrahydrofuran; toluene / 1 h / -78 °C 5: NaN(SiMe3)2 / tetrahydrofuran / 3 h / 0 °C View Scheme
Multi-step reaction with 4 steps 1.1: sodium hydride; zinc(II) chloride / mineral oil; tetrahydrofuran / 0.42 h / 25 - 35 °C / Inert atmosphere 1.2: 2.08 h / 25 - 40 °C / Inert atmosphere 2.1: diethylamino-sulfur trifluoride / dichloromethane / 24 h / 0 - 35 °C / Inert atmosphere 3.1: diisobutylaluminium hydride / toluene / 3.25 h / -65 - -61 °C / Inert atmosphere 4.1: sodium hexamethyldisilazane / tetrahydrofuran / 0.67 h / 5 °C / Inert atmosphere 4.2: 2 h / 0 - 3 °C View Scheme
Multi-step reaction with 5 steps 1: lithium hydroxide monohydrate / tetrahydrofuran; water / 1 h / 20 °C 2: diethylamino-sulfur trifluoride / dichloromethane / 72 h / 20 °C 3: potassium carbonate / methanol / 1.5 h / 20 °C 4: diisobutylaluminium hydride / tetrahydrofuran; hexane / 0.5 h / -70 °C 5: sodium hexamethyldisilazane / tetrahydrofuran / 2 h / 0 - 10 °C View Scheme

dimethyl (3-phenoxy-2-oxopropyl)phosphonate (40665-68-7) → tafluprost

Conditions	Yield
Multi-step reaction with 6 steps 1: NaH 2: morpholinosulfur trifluoride / CHCl3 / 82 h / 30 - 40 °C 3: K2CO3 / methanol / 3 h / 20 °C 4: 83 percent / diisobutylaluminum hydride / tetrahydrofuran; toluene / 1 h / -78 °C 5: NaN(SiMe3)2 / tetrahydrofuran / 3 h / 0 °C 6: 1,8-diazabicyclo[5.4.0]undec-7-ene / acetone / 16 h / 20 °C View Scheme
Multi-step reaction with 6 steps 1: 90 percent / NaH 2: morpholinosulfur trifluoride / CHCl3 / 82 h / 30 - 40 °C 3: K2CO3 / methanol / 3 h / 20 °C 4: 83 percent / diisobutylaluminum hydride / tetrahydrofuran; toluene / 1 h / -78 °C 5: NaN(SiMe3)2 / tetrahydrofuran / 3 h / 0 °C 6: 1,8-diazabicyclo[5.4.0]undec-7-ene / acetone / 16 h / 20 °C View Scheme
Multi-step reaction with 6 steps 1.1: sodium hydride; zinc(II) chloride / mineral oil; tetrahydrofuran / 0.42 h / 25 - 35 °C / Inert atmosphere 1.2: 2.08 h / 25 - 40 °C / Inert atmosphere 2.1: diethylamino-sulfur trifluoride / dichloromethane / 24 h / 0 - 35 °C / Inert atmosphere 3.1: diisobutylaluminium hydride / toluene / 3.25 h / -65 - -61 °C / Inert atmosphere 4.1: sodium hexamethyldisilazane / tetrahydrofuran / 0.67 h / 5 °C / Inert atmosphere 4.2: 2 h / 0 - 3 °C 5.1: acetone / 20 °C 6.1: sulfuric acid / ethyl acetate 6.2: 20 h / 30 °C View Scheme

Upstream product

• 701-99-5 Phenoxyacetyl chloride 
• 756-79-6 dimethyl methane phosphonate 
• 2555-49-9 phenoxyacetic acid ethyl ester 
• 122-60-1 Phenyl glycidyl ether 
• 108-95-2 phenol 
• 709-84-2 bis-tetrahydropyran-2-yl ether 
• 109-72-8 n-butyllithium 
• 2065-23-8 methyl 2-phenoxyacetate 
• 34939-91-8 dimethyl lithiomethylphosphonate 

Downstream Products

• 111803-58-8 Biphenyl-4-carboxylic acid (3aS,5S,6aR)-2-oxo-4-((E)-3-oxo-4-phenoxy-but-1-enyl)-octahydro-cyclopenta[b]pyrrol-5-yl ester 
• 141242-73-1 C₇₃H₁₁₈O₁₈Si₃ 
• 62561-47-1 16-phenoxy-17,18,19,20-tetranor-15-dehydroprostaglandin F_2α 9-acetate methyl ester 11-(tetrahydropyran-2-yl ether) 
• 131846-19-0 methyl 1-homo-3,4-cis-didehydro-9,15-diketo-16-phenoxy-17,18,19,20-tetranorprostenoate 
• 122437-70-1 methyl 9,15-dioxo-16-phenoxy-13-trans-17,18,19,20-tetranorprostenoate 
• 87929-54-2 (Z)-7-[(1S,2R,3S,4R)-3-((E)-3-Oxo-4-phenoxy-but-1-enyl)-7-oxa-bicyclo[2.2.1]hept-2-yl]-hept-5-enoic acid methyl ester 
• 871669-30-6 7α-trimethylsilyloxy-6β-(3'-oxo-4'-phenoxy-1'E-butenyl)-2-oxabicyclo<3.3.0>octan-3-one 
• 871669-32-8 7α-hydroxy-6β-(3'-oxo-4'-phenoxy-1'E-butenyl)-2-oxabicyclo<3.3.0>octan-3-one 

Relevant articles and documents

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