848609-05-2

Basic information

• Product Name: 1-Decyn-5-ol,(5S)-
• Synonyms: 1-Decyn-5-ol,(5S)-;(5S)-1-Decyn-5-ol;(S)-dec-1-yn-5-ol;(5S)-dec-1-yn-5-ol;1-Decyn-5-ol
• CAS NO: 848609-05-2
• Molecular Formula: C₁₀H₁₈O
• Molecular Weight: 154.24932
• Product Categories: Treprostinil
• Mol File: 848609-05-2.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 241.3±13.0 °C(Predicted)
• Appearance: /
• Density: 0.880±0.06 g/cm3(Predicted)
• PKA: 15.02±0.20(Predicted)
• CAS DataBase Reference: 1-Decyn-5-ol,(5S)-(CAS DataBase Reference)
• NIST Chemistry Reference: 1-Decyn-5-ol,(5S)-(848609-05-2)
• EPA Substance Registry System: 1-Decyn-5-ol,(5S)-(848609-05-2)

Safety Data

• Hazardous Substances Data: 848609-05-2(Hazardous Substances Data)

Usage

General Description

1-Decyn-5-ol, (5S)- is a chemical compound noted for its unique structure. It belongs to the class of organic compounds known as fatty alcohols. These are aliphatic alcohols consisting of a chain of a given number of carbon atoms to which a hydroxyl (-OH) group is attached. In the case of 1-Decyn-5-ol, this chain contains ten carbon atoms, with a carbon-carbon triple bond (C≡C) located between the first and second carbons, and a hydroxyl group attached to the fifth carbon, denoted by its name.

Synthetic route

(S)-dec-2-yn-5-ol → (S)-Dec-1-yn-5-ol (848609-05-2)

Conditions	Yield
Stage #1: (S)-dec-2-yn-5-ol With potassium tert-butylate; lithium; Trimethylenediamine In diethyl ether at 20 - 70℃; for 2.33333h; Stage #2: With water In diethyl ether at 0℃;	n/a

(S)-1-chloroheptane-2-ol (81007-64-9) → (S)-Dec-1-yn-5-ol (848609-05-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium hydroxide / tert-butyl methyl ether / 18 h / 25 °C 2.1: magnesium; iodine; mercury dichloride / diethyl ether / 0 - 36 °C / Inert atmosphere 2.2: 0.5 h View Scheme
Multi-step reaction with 3 steps 1.1: sodium hydroxide / tert-butyl methyl ether / 18 h / 25 °C 2.1: n-butyllithium / tetrahydrofuran; hexane / 3.5 h / -50 - -35 °C / Inert atmosphere 2.2: 2.5 h / -40 - -20 °C 3.1: sodium hydroxide; ethanol / 2 h / 25 °C View Scheme
Multi-step reaction with 2 steps 1.1: potassium hydroxide / dichloromethane / 3 h / 20 °C / Cooling with ice 2.1: mercury dichloride; magnesium; iodine / diethyl ether / Inert atmosphere 2.2: 2 h / 20 °C / Inert atmosphere View Scheme

(S)-2-pentyloxirane (61229-03-6) → (S)-Dec-1-yn-5-ol (848609-05-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: n-butyllithium / tetrahydrofuran; hexane / 3.5 h / -50 - -35 °C / Inert atmosphere 1.2: 2.5 h / -40 - -20 °C 2.1: sodium hydroxide; ethanol / 2 h / 25 °C View Scheme

(S)-2-pentyloxirane (61229-03-6) + propargyl bromide (106-96-7) → (S)-Dec-1-yn-5-ol (848609-05-2)

Conditions	Yield
Stage #1: propargyl bromide With iodine; magnesium; mercury dichloride In diethyl ether at 0 - 36℃; Inert atmosphere; Stage #2: (S)-2-pentyloxirane In diethyl ether for 0.5h;	62.9 g
Stage #1: propargyl bromide With iodine; magnesium; mercury dichloride In diethyl ether Inert atmosphere; Stage #2: (S)-2-pentyloxirane In diethyl ether at 20℃; for 2h; Inert atmosphere;	10.2 g

C13H26OSi → (S)-Dec-1-yn-5-ol (848609-05-2)

Conditions	Yield
With ethanol; sodium hydroxide at 25℃; for 2h;	73.9 g

(S)-Dec-1-yn-5-ol (848609-05-2) + tert-butylchlorodiphenylsilane (58479-61-1) → (S)-tert-butyl(dec-1-yn-5-yloxy)diphenylsilane

Conditions	Yield
Stage #1: (S)-Dec-1-yn-5-ol With dmap In dichloromethane; N,N-dimethyl-formamide at 20 - 250℃; for 0.333333h; Stage #2: tert-butylchlorodiphenylsilane In dichloromethane; N,N-dimethyl-d6-formamide at 20℃; for 12h;	89%

3,4-dihydro-2H-pyran (110-87-2) + (S)-Dec-1-yn-5-ol (848609-05-2) → 2-[[(1S)-1-(3-butynyl)hexyl]oxy]tetrahydro-2H-pyran (223734-62-1)

Conditions	Yield
With pyridinium p-toluenesulfonate In dichloromethane at 0 - 25℃; for 24h; Temperature;	65.1 g

(S)-Dec-1-yn-5-ol (848609-05-2) → (6S)-1-(2-allyl-3-(benzyloxy)phenyl)-6-((tetrahydro-2H-pyran-2-yl)oxy)undec-2-yn-1-one

Conditions	Yield
Multi-step reaction with 2 steps 1.1: pyridinium p-toluenesulfonate / dichloromethane / 24 h / 0 - 25 °C 2.1: ethylmagnesium bromide / tetrahydrofuran; diethyl ether / 35 - 40 °C 2.2: 1 h / 25 °C / Reflux View Scheme

(S)-Dec-1-yn-5-ol (848609-05-2) → tert-butyl 2-(2-allyl-3-((6S)-6-((tert-butyldiphenylsilyl)oxy)-1-hydroxyundec-2-yn-1-yl)phenoxy)acetate

Conditions	Yield
Multi-step reaction with 2 steps 1.1: dmap / dichloromethane; N,N-dimethyl-formamide / 0.33 h / 20 - 250 °C 1.2: 12 h / 20 °C 2.1: ethylmagnesium bromide / tetrahydrofuran; diethyl ether / 1.5 h / Inert atmosphere; Reflux 2.2: 12 h / 0 - 20 °C / Inert atmosphere View Scheme

(S)-Dec-1-yn-5-ol (848609-05-2) → tert-butyl (S)-2-(2-allyl-3-(6-((tert-butyldiphenylsilyl)oxy)undec-2-ynoyl)phenoxy)acetate

Conditions	Yield
Multi-step reaction with 3 steps 1.1: dmap / dichloromethane; N,N-dimethyl-formamide / 0.33 h / 20 - 250 °C 1.2: 12 h / 20 °C 2.1: ethylmagnesium bromide / tetrahydrofuran; diethyl ether / 1.5 h / Inert atmosphere; Reflux 2.2: 12 h / 0 - 20 °C / Inert atmosphere 3.1: manganese(IV) oxide / acetone / 24 h / 0 - 20 °C View Scheme

(S)-Dec-1-yn-5-ol (848609-05-2) → tert-butyl 2-(2-allyl-3-((1S,6S)-6-((tert-butyldiphenylsilyl)oxy)-1-hydroxyundec-2-yn-1-yl)phenoxy)acetate

Conditions

Yield

Multi-step reaction with 4 steps 1.1: dmap / dichloromethane; N,N-dimethyl-formamide / 0.33 h / 20 - 250 °C 1.2: 12 h / 20 °C 2.1: ethylmagnesium bromide / tetrahydrofuran; diethyl ether / 1.5 h / Inert atmosphere; Reflux 2.2: 12 h / 0 - 20 °C / Inert atmosphere 3.1: manganese(IV) oxide / acetone / 24 h / 0 - 20 °C 4.1: dimethylsulfide borane complex / tetrahydrofuran / 1 h / -30 °C / Inert atmosphere View Scheme

(S)-Dec-1-yn-5-ol (848609-05-2) → tert-butyl 2-(2-allyl-3-((1S,6S)-6-tert-butyldiphenylsilyloxy-1-tert-butyldimethylsilyloxyundec-2-yn-1-yl)phenoxy)acetate

Conditions

Yield

Multi-step reaction with 5 steps 1.1: dmap / dichloromethane; N,N-dimethyl-formamide / 0.33 h / 20 - 250 °C 1.2: 12 h / 20 °C 2.1: ethylmagnesium bromide / tetrahydrofuran; diethyl ether / 1.5 h / Inert atmosphere; Reflux 2.2: 12 h / 0 - 20 °C / Inert atmosphere 3.1: manganese(IV) oxide / acetone / 24 h / 0 - 20 °C 4.1: dimethylsulfide borane complex / tetrahydrofuran / 1 h / -30 °C / Inert atmosphere 5.1: dmap; 1H-imidazole / dichloromethane; N,N-dimethyl-formamide / 15 h / 0 - 20 °C / Inert atmosphere View Scheme

(S)-Dec-1-yn-5-ol (848609-05-2) → tert-butyl 2-(((4R,9aS)-4-((tert-butyldimethylsilyl)oxy)-3-((S)-3-((tert-butyldiphenylsilyl)oxy)octyl)-2-oxo-2,4,9,9a-tetrahydro-1H-cyclopenta[b]naphthalen-8-yl)oxy)acetate

Conditions

Yield

Multi-step reaction with 6 steps 1.1: dmap / dichloromethane; N,N-dimethyl-formamide / 0.33 h / 20 - 250 °C 1.2: 12 h / 20 °C 2.1: ethylmagnesium bromide / tetrahydrofuran; diethyl ether / 1.5 h / Inert atmosphere; Reflux 2.2: 12 h / 0 - 20 °C / Inert atmosphere 3.1: manganese(IV) oxide / acetone / 24 h / 0 - 20 °C 4.1: dimethylsulfide borane complex / tetrahydrofuran / 1 h / -30 °C / Inert atmosphere 5.1: dmap; 1H-imidazole / dichloromethane; N,N-dimethyl-formamide / 15 h / 0 - 20 °C / Inert atmosphere 6.1: dicobalt octacarbonyl / toluene / 170 °C / 15001.5 Torr / Flow reactor View Scheme

(S)-Dec-1-yn-5-ol (848609-05-2) → tert-butyl 2-(((3aS,9aS)-1-((S)-3-((tert-butyldiphenylsilyl)oxy)octyl)-2-oxo-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]naphthalen-5-yl)oxy)acetate

Conditions

Yield

Multi-step reaction with 7 steps 1.1: dmap / dichloromethane; N,N-dimethyl-formamide / 0.33 h / 20 - 250 °C 1.2: 12 h / 20 °C 2.1: ethylmagnesium bromide / tetrahydrofuran; diethyl ether / 1.5 h / Inert atmosphere; Reflux 2.2: 12 h / 0 - 20 °C / Inert atmosphere 3.1: manganese(IV) oxide / acetone / 24 h / 0 - 20 °C 4.1: dimethylsulfide borane complex / tetrahydrofuran / 1 h / -30 °C / Inert atmosphere 5.1: dmap; 1H-imidazole / dichloromethane; N,N-dimethyl-formamide / 15 h / 0 - 20 °C / Inert atmosphere 6.1: dicobalt octacarbonyl / toluene / 170 °C / 15001.5 Torr / Flow reactor 7.1: potassium carbonate; palladium 10% on activated carbon; hydrogen / ethanol / 15 h / 20 °C / 2250.23 Torr View Scheme

(S)-Dec-1-yn-5-ol (848609-05-2) → 2-(((1R,2R,3aS,9aS)-1-((S)-3-((tert-butyldiphenylsilyl)oxy)octyl)-2-hydroxy-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]naphthalen-5-yl)oxy)acetic acid

Conditions

Yield

Multi-step reaction with 8 steps 1.1: dmap / dichloromethane; N,N-dimethyl-formamide / 0.33 h / 20 - 250 °C 1.2: 12 h / 20 °C 2.1: ethylmagnesium bromide / tetrahydrofuran; diethyl ether / 1.5 h / Inert atmosphere; Reflux 2.2: 12 h / 0 - 20 °C / Inert atmosphere 3.1: manganese(IV) oxide / acetone / 24 h / 0 - 20 °C 4.1: dimethylsulfide borane complex / tetrahydrofuran / 1 h / -30 °C / Inert atmosphere 5.1: dmap; 1H-imidazole / dichloromethane; N,N-dimethyl-formamide / 15 h / 0 - 20 °C / Inert atmosphere 6.1: dicobalt octacarbonyl / toluene / 170 °C / 15001.5 Torr / Flow reactor 7.1: potassium carbonate; palladium 10% on activated carbon; hydrogen / ethanol / 15 h / 20 °C / 2250.23 Torr 8.1: sodium hydroxide / ethanol; water / 0.5 h / -10 °C 8.2: 13 h / -10 - 0 °C View Scheme

(S)-Dec-1-yn-5-ol (848609-05-2) → treprostinil (81846-19-7)

Conditions

Yield

Multi-step reaction with 9 steps 1.1: dmap / dichloromethane; N,N-dimethyl-formamide / 0.33 h / 20 - 250 °C 1.2: 12 h / 20 °C 2.1: ethylmagnesium bromide / tetrahydrofuran; diethyl ether / 1.5 h / Inert atmosphere; Reflux 2.2: 12 h / 0 - 20 °C / Inert atmosphere 3.1: manganese(IV) oxide / acetone / 24 h / 0 - 20 °C 4.1: dimethylsulfide borane complex / tetrahydrofuran / 1 h / -30 °C / Inert atmosphere 5.1: dmap; 1H-imidazole / dichloromethane; N,N-dimethyl-formamide / 15 h / 0 - 20 °C / Inert atmosphere 6.1: dicobalt octacarbonyl / toluene / 170 °C / 15001.5 Torr / Flow reactor 7.1: potassium carbonate; palladium 10% on activated carbon; hydrogen / ethanol / 15 h / 20 °C / 2250.23 Torr 8.1: sodium hydroxide / ethanol; water / 0.5 h / -10 °C 8.2: 13 h / -10 - 0 °C 9.1: pyridine; pyridine hydrogenfluoride / 15 h / 20 °C / Cooling View Scheme

Upstream product

• 61229-03-6 (S)-2-pentyloxirane 
• 106-96-7 propargyl bromide 
• 81007-64-9 (S)-1-chloroheptane-2-ol 

Downstream Products

• 223734-62-1 2-[[(1S)-1-(3-butynyl)hexyl]oxy]tetrahydro-2H-pyran 
• 81846-19-7 treprostinil 

Relevant articles and documents

The curved front row neil intermediate preparation method

The invention relates to a preparation method for a treprostinil intermediate (I). The preparation method comprises the steps that: a compound of a formula (II) and a compound of a formula (III) or acidic salt thereof react in the presence of a condensing agent to obtain a compound of a formula (IV); the compound of the formula (IV) and a compound of a formula (V) react to obtain a compound of a formula (I). According to the preparation method for the treprostinil intermediate, weinreb amide and alkyne negative ions react to directly obtain a ketone compound (I), so that environment pollution caused by heavy metal (a PCC oxidant) is avoided, and the adoption of a butyl lithium low-temperature reaction method is also avoided. The preparation method for the treprostinil intermediate has the advantages that reaction conditions are mild, the yield is high, the purity of products is high, and the industrial application prospect is wide. (Formulae (I), (II), (III), (IV) and (V) are shown in the specification)

Method of preparation of an alkyne with an optically active hydroxyl group in the beta or gamma position of a triple bond and intermediates obtained

The present invention relates to a method of preparation of an alkyne with an optically active hydroxyl group in the β or γ position of a triple bond and intermediates obtained. The method of the invention for preparation of an alkyne with an optically active hydroxyl group in the β position of a triple bond is characterized in that it comprises the reaction, in the presence of a Lewis acid: of a compound of formula (IV): in which: R is a linear or branched alkyl group having from 1 to 6 carbon atoms. and of a compound of formula (V): [in-line-formulae]R′—C≡C-M ??(V) [/in-line-formulae]in which: R′ represents a hydrogen atom, a linear or branched alkyl group having from 1 to 8 carbon atoms, preferably a methyl group or a trialkylsilyl group. M represents a metal, preferably a metal of group (Ia) of the periodic table, preferably lithium. Another object of the invention comprises the production of an alkyne with an optically active hydroxyl group in the γ position of a triple bond by isomerization of an alkyne with an optically active hydroxyl group in the β position previously obtained.