68641-49-6

Basic information

• Product Name: Bis(2-oxo-3-oxazolidinyl)phosphinic chloride
• Synonyms: bis(2-oxo-3-oxazolidinyl)-phosphinicchlorid;PHOSPHORIC ACID BIS(2-OXOOXAZOLIDIDE) CHLORIDE;N,N-BIS(2-OXO-3-OXAZOLIDINYL)PHOSPHINIC CHLORIDE;N,N-BIS(2-OXO-3-OXAZOLIDINYL)PHOSPHONIC CHLORIDE;N,N-BIS(2-OXO-3-OXAZOLIDINYL)PHOSPHORODIAMIDIC CHLORIDE;BIS(2-OXO-3-OXAZOLIDINYL)PHOSPHINIC CHLORIDE;BIS(2-OXO-3-OXAZOLIDINYL)PHOSPHONIC CHLORIDE;BIS(2-OXO-3-OXAZOLIDINYL)PHOSPHORODIAMIDIC CHLORIDE
• CAS NO: 68641-49-6
• Molecular Formula: C₆H₈ClN₂O₅P
• Molecular Weight: 254.56
• EINECS: 1533716-785-6
• Product Categories: Peptide coupling agents;Coupling Reagent;Biochemistry;Condensation & Active Esterification;Coupling Reactions (Peptide Synthesis);Peptide Synthesis;Synthetic Organic Chemistry
• Mol File: 68641-49-6.mol
• Article Data: 7

Chemical Properties

• Melting Point: 191 °C (dec.)(lit.)
• Boiling Point: 332.8 °C at 760 mmHg
• Flash Point: 155.1 °C
• Appearance: White to off-white/Crystalline Powder
• Density: 1.71 g/cm³
• Vapor Pressure: 0.000142mmHg at 25°C
• Refractive Index: 1.572
• Storage Temp.: Store at RT.
• PKA: -2.47±0.20(Predicted)
• Water Solubility: Hydrolyzes with water.
• Sensitive: Moisture Sensitive
• BRN: 3654596
• CAS DataBase Reference: Bis(2-oxo-3-oxazolidinyl)phosphinic chloride(CAS DataBase Reference)
• NIST Chemistry Reference: Bis(2-oxo-3-oxazolidinyl)phosphinic chloride(68641-49-6)
• EPA Substance Registry System: Bis(2-oxo-3-oxazolidinyl)phosphinic chloride(68641-49-6)

Safety Data

• Hazard Codes: C
• Statements: 34
• Safety Statements: 26-36/37/39-45-27
• RIDADR: UN 3261 8/PG 2
• WGK Germany: 3
• RTECS: SZ5871000
• F: 10-21
• HazardClass: 8
• PackingGroup: II
• Hazardous Substances Data: 68641-49-6(Hazardous Substances Data)

Usage

Chemical Properties

White solid

Uses

Bis(2-oxo-3-oxazolidinyl)phosphinic chloride was used in the preparation of hexadepsipeptide.

InChI:InChI=1/C6H8ClN2O5P/c7-15(12,8-1-3-13-5(8)10)9-2-4-14-6(9)11/h1-4H2

Synthetic route

C24H24ClN2O9P*C5H5N (77349-88-3) + aniline (62-53-3) → bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride (68641-49-6) + Phenyl-acetic acid indan-5-yl ester (77331-11-4) + 2,N-Diphenyl-malonamic acid indan-5-yl ester (59858-31-0)

Conditions	Yield
	A 19% B 26% C 73%

dimethylenecyclourethane (497-25-6) → bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride (68641-49-6)

Conditions	Yield
With phosphorus pentachloride In nitromethane at 20℃; for 4h; phosphoramidation;	60%
With phosphorus pentachloride; water 1.) acetonitrile, 20-25 deg C, 24 h 2.) 15-20 deg C, 30 min; Yield given. Multistep reaction;
With phosphorus pentachloride; water 1.) nitromethane, 20-25 deg C, 4 h; 40-45 deg C, 2 h; 2.) nitromethane, 1,2-dimethoxyethane, 0 deg C, 5 min.; Yield given. Multistep reaction;
With phosphorus pentachloride; water 1.) MeCN, 24 h, room temp. 2.) MeCN, -5 deg C; Yield given. Multistep reaction;
With triethylamine; trichlorophosphate In tetrahydrofuran at 0 - 35℃; for 2h;

bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride (68641-49-6) + N-butylamine (109-73-9) → C10H18N3O5P (91775-41-6)

Conditions	Yield
In dichloromethane for 0.75h; Ambient temperature;	100%
With triethylamine In dichloromethane at 20 - 25℃; for 0.75h;	100%

BOC-glycine (4530-20-5) + bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride (68641-49-6) → (R*)-N-[[2-[N-[(1,1-Dimethylethoxy)carbonyl]glycyl]-1,2,3,4-tetrahydro-3-isoquinolinyl]carbonyl]-L-methionine

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane	100%

bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride (68641-49-6) + tert-butylamine (75-64-9) → C10H18N3O5P (91775-43-8)

Conditions	Yield
In dichloromethane at 20 - 25℃; for 3.5h;	99%

L-N-Boc-Ala (15761-38-3) + bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride (68641-49-6) → (R*)-N-[[2-[N-[(1,1-Dimethylethoxy)carbonyl]-L-alanyl]-1,2,3,4-tetrahydro-3-isoquinolinyl]carbonyl]-L-methionine

Conditions	Yield
With hydrogenchloride; N-ethyl-N,N-diisopropylamine In 1,4-dioxane; dimethylsulfide; dichloromethane	99%

t-Butyloxycarbonyl-L-1,2,3,4-tetrahydroisoquinolin-3-carboxylic acid + bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride (68641-49-6) → (R*)-N-[[2-[(1,1-Dimethylethoxy)carbonyl]-1,2,3,4-tetrahydro-3-isoquinolinyl]carbonyl]-N-methyl-L-methionine

Conditions	Yield
With hydrogenchloride; N-ethyl-N,N-diisopropylamine In 1,4-dioxane; dimethylsulfide; dichloromethane	99%

bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride (68641-49-6) + 2,6-dichlorobenzoic acid N-ethyl-piperidinium salt (81592-01-0) → C13H11Cl2N2O7P (77331-22-7)

Conditions	Yield
	98%

bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride (68641-49-6) + 2,6-dichlorobenzoic acid (50-30-6) → C13H11Cl2N2O7P (77331-22-7)

Conditions	Yield
With 1-ethyl-piperidine In dichloromethane at 15℃; for 1.5h;	98%

C13H19BrO3Si (1477517-16-0) + bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride (68641-49-6) → C19H26BrN2O8PSi (1477517-17-1)

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 1h;	98%

bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride (68641-49-6) + 2,6-dimethoxybenzoic acid triethylammonium salt (77331-14-7) → C15H18ClN2O9P*C6H15N (77331-20-5)

Conditions	Yield
In hexane; dichloromethane at 20℃; for 0.5h;	97%

bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride (68641-49-6) → N,N-bis<2-oxo-3-oxazolidinyl>phosphorodiamidic azide

Conditions	Yield
With sodium azide In nitromethane at 70℃; for 3h;	97%

bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride (68641-49-6) + n-allylcyclopentylamine (55611-39-7) + 3-chloro-5-(tert-butyldimethylsilyloxy)benzoic acid (245116-08-9) → [3-Chloro-5-(tert-butyldimethylsilyloxy)phenyl]-N-cyclopentyl-N-prop-2-enylcarboxamide

Conditions	Yield
With triethylamine In dichloromethane	97%

t-Boc-L-valine (13734-41-3) + bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride (68641-49-6) → (R*)-N-[[2-[N-[(1,1-Dimethylethoxy)-carbonyl]-L-valyl]-1,2,3,4-tetrahydro-3-isoquinolinyl]carbonyl]-L-methionine

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane	97%
With N-ethyl-N,N-diisopropylamine In dichloromethane

BOP chloride + t-Boc-L-valine (13734-41-3) + bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride (68641-49-6) → (R*)-N-[[2-[N-[(1,1-Dimethylethoxy)-carbonyl]-L-valyl]-1,2,3,4-tetrahydro-3-isoquinolinyl]carbonyl]-L-methionine

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane	97%

p-cresol (106-44-5) + bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride (68641-49-6) → p-tolyl bis(2-oxo-3-oxazolidinyl)phosphoramide (1231261-79-2)

Conditions	Yield
With dmap; triethylamine In dichloromethane at 20℃; Inert atmosphere;	97%

C12H16F3NO7S + bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride (68641-49-6) → C24H28F6N2O12S2

Conditions	Yield
With 2,4,6-trimethyl-pyridine In dichloromethane at 0 - 25℃; for 26h; Inert atmosphere; Sealed tube;	97%

4-nitro-phenol (100-02-7) + bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride (68641-49-6) → (2-oxo-3-oxazolidinyl)p-nitrophenyl phosphoramidate

Conditions	Yield
With triethylamine In dichloromethane at 20 - 25℃;	96%

(2R*,4S*)-2-benzyl-N-(4-quinolylmethyl)-N-trifluoroacetyl-4-piperidinamine + 3-Cyanobenzoic acid (1877-72-1) + bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride (68641-49-6) → (2R*,4S*)-2-benzyl-1-(3-cyanobenzoyl)-N-(4-quinolylmethyl)-N-trifluoroacetyl-4-piperidinamine

Conditions	Yield
With triethylamine	96%

bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride (68641-49-6) + 2-Phenyl-malonic acid mono-indan-5-yl ester; compound with pyridine (77331-12-5) → C24H24ClN2O9P*C5H5N (77349-88-3)

Conditions	Yield
In acetonitrile at -15℃; for 0.5h;	95%

bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride (68641-49-6) + β-naphthol (135-19-3) → naphthalen-2-yl bis(2-oxo-3-oxazolidinyl)phosphoramide (1231261-76-9)

Conditions	Yield
With dmap; triethylamine In dichloromethane at 20℃; Inert atmosphere;	95%
With triethylamine In dichloromethane at 0 - 20℃; Inert atmosphere;	62%

2-bromo-3-hydroxy-benzaldehyde (196081-71-7) + bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride (68641-49-6) → C13H12BrN2O7P (1477517-12-6)

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 1h;	94%

bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride (68641-49-6) + 2-Phenyl-malonic acid monophenyl ester; compound with pyridine (77331-13-6) → C21H20ClN2O9P*C5H5N (77331-18-1)

Conditions	Yield
In acetonitrile at -15℃; for 0.5h;	93%

t-Boc-L-valine (13734-41-3) + bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride (68641-49-6) → (R*)-2-[N-[(1,1-Dimethylethoxy)carbonyl]-L-valyl]-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid, phenylmethyl ester

Conditions	Yield
With hydrogenchloride; sodium hydrogencarbonate; N-ethyl-N,N-diisopropylamine In dichloromethane; water; ethyl acetate	93%

bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride (68641-49-6) + 4-Hydroxyacetophenone (99-93-4) → 4-acetylphenyl bis(2-oxo-3-oxazolidinyl)phosphoramide (1231261-83-8)

Conditions	Yield
With dmap; triethylamine In dichloromethane at 20℃; Inert atmosphere;	93%

4-Fluorophenol (371-41-5) + bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride (68641-49-6) → 4-fluorophenyl bis(2-oxo-3-oxazolidinyl)phosphoramide (1231261-81-6)

Conditions	Yield
With dmap; triethylamine In dichloromethane at 20℃; Inert atmosphere;	92%

bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride (68641-49-6) + 4-cyanophenol (767-00-0) → 4-cyanophenyl bis(2-oxo-3-oxazolidinyl)phosphoramide (1231261-82-7)

Conditions	Yield
With dmap; triethylamine In dichloromethane at 20℃; Inert atmosphere;	92%

bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride (68641-49-6) + 3-Dimethylaminophenol (99-07-0) → 3-(dimethylamino)phenyl bis(2-oxo-3-oxazolidinyl)phosphoramide (1231261-80-5)

Conditions	Yield
With dmap; triethylamine In dichloromethane at 20℃; Inert atmosphere;	92%

1-bromo-2-naphthol (573-97-7) + bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride (68641-49-6) → C16H14BrN2O6P (1477517-11-5)

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 1h;	92%

bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride (68641-49-6) + phenethylamine (64-04-0) → N,N-Bis(2-oxo-oxozolidinyl)-N-β-phenylethylphosphorotriamide (91747-68-1)

Conditions	Yield
With triethylamine In dichloromethane at 20 - 25℃; for 0.25h;	91%

6-cyano-2-naphthol (52927-22-7) + bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride (68641-49-6) → 6-cyanonaphthalen-2-yl bis(2-oxo-3-oxazolidinyl)phosphoramide (1231261-78-1)

Conditions	Yield
With dmap; triethylamine In dichloromethane at 20℃; Inert atmosphere;	91%

L-leucine tert-butyl ester (21691-53-2) + bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride (68641-49-6) → C16H28N3O7P

Conditions	Yield
With N-ethyl-N,N-diisopropylamine at 0℃; for 4h;	90%

Upstream product

• 497-25-6 dimethylenecyclourethane 
• 77349-88-3 C₂₄H₂₄ClN₂O₉P*C₅H₅N 
• 62-53-3 aniline 

Downstream Products

• 77331-21-6 2,6-Dinitrobenzoyl N,N-bis<2-oxo-3-oxazolidinyl>phosphorodiamidate 
• 367261-68-5 2-[(2S)-2-(3,4-dichlorophenyl)pent-4-enyl]-1-oxo-1,2,3,4-tetrahydronaphtho[1,2-f][1,4]thiazepine-6-carbonitrile 
• 185212-13-9 1-(N-benzyloxycarbonyl-2(S)-aminobutyryl)-3,3-dimethylindoline-2(R/S)-carboxylic Acid Butylamide 
• 254882-54-7 N-tert-butoxycarbonyl-D-homophenylalanine 3-quinolylamide 
• 208847-40-9 (Pyrrole-2-carbonyl)-N-(benzyl)glycine-t-butyl ester 
• 1238376-61-8 2-[(N-tert-butoxycarbonyl-4(R)-benzyloxy)-L-prolyl]1,2,3,4-tetrahydro-9H-pyrido[3,4-b ]indole 
• 133073-35-5 benzyloxycarbonyl-L-valyl-N-cyclopentylglycine t-butyl ester 
• 135497-22-2 N-t-Butyloxycarbonyl-(O-benzyl)-R-tyrosine-di-n-pentylamide 
• 135497-21-1 N-(t-Butyloxycarbonyl)-R-tyrosine-di-n-pentylamide 
• 135497-13-1 N-(t-Butyloxycarbonyl)-(2R,3S)-(O-benzyl)threonine-di-n-pentylamide 
• 139422-30-3 methyl 4-chloro-2-(pyridin-3-yl)acetamidobenzoate 
• 166337-42-4 N‐methoxy‐N‐methyl‐2‐phenyl butyramide 
• 91481-25-3 2-amino-2-(3,4-dichlorophenyl)acetonitrile 

Relevant articles and documents

2-Naphthol as a powerful chromophore for the configurational assignment of carboxylic acid groups via the CD exciton chirality method

A novel approach for the stereochemical assignment of carboxylic acid groups via the circular dichroism (CD) exciton chirality method using the 2- naphthyl chromophore is described. Direct esterification of carboxyl groups with 2-naphthol was effectively achieved with the employment of N,N-bis[2- oxo-3-oxazolidinyl]phosphorodiamidic chloride as the activating reagent. The method was tested with several model compounds, including both cyclic and acyclic dicarboxylic acids, and also applied to the natural product abietic acid. (C) 2000 Elsevier Science Ltd.

Non-Imuunosuppressive cyclosporins and their use in the prevention and treatment of HIV infection

Disclosed are cyclosporin analogs having amino acid residue substitutions at positions 1, 3, or 7 of the cyclosporin peptide backbone. Also disclosed are conjugates of these cyclosporin analogs in which an HIV protease inhibitor moiety is conjugated to the position-7 amino acid residue of the cyclosporin. These compounds simultaneously bind to and inhibit cyclophilin and HIV protease. The compounds have good bioavailability and potent HIV inhibitory activity. They are useful in the treatment and prevention of HIV-mediated disorders, including AIDS.

Convenient Synthesis of Carboxylic Acid Anhydrides using N,N-Bisphosphorodiamidic Chloride

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