1070-65-1

Usage

InChI:InChI=1/C10H19ClO3/c1-2-14-10(13)6-4-3-5-9(12)7-8-11/h9,12H,2-8H2,1H3

Synthetic route

adipinic acid monoethyl ester (626-86-8) → 6-hydroxy-8-chlorooctanoic acid ethyl ester (1070-65-1)

Conditions	Yield
With thionyl chloride; 1,1,2,2-tetrachloroethane anschliessendes Behandeln mit Aethylen und Aluminiumchlorid und Behandeln der nach dem Versetzen mit wss.Salzsaeure erhaltenen nicht-waessrigen Phase des Reaktionsgemisches mit Natriumboranat in Aethanol;

ethyl 6-oxo-8-chlorooctanoate → 6-hydroxy-8-chlorooctanoic acid ethyl ester (1070-65-1)

Conditions	Yield
With sodium tetrahydroborate; tetrabutylammomium bromide; ammonia In 1,2-dichloro-ethane at 10 - 30℃; for 2h; Large scale;	95 kg

6-hydroxy-8-chlorooctanoic acid ethyl ester (1070-65-1) → 6,8-dichlorooctanoic acid ethyl ester (1070-64-0)

Conditions	Yield
With phosgene; N,N'-dimethylbenzylamine In 1,2-dichloro-ethane at 10 - 75℃; for 2.5h; Concentration; Solvent; Reagent/catalyst; Temperature;	96.69%
With pyridine; thionyl chloride; benzene
With thionyl chloride In toluene at 100℃; for 5h; Reagent/catalyst; Solvent; Cooling with ice; Large scale;	480 kg

6-hydroxy-8-chlorooctanoic acid ethyl ester (1070-65-1) → (+)-8-chloro-6-hydroxy-octanoic acid (90435-60-2)

Conditions	Yield
With lithium hydroxide In ethanol Ambient temperature; Yield given;

6-hydroxy-8-chlorooctanoic acid ethyl ester (1070-65-1) → N-(3-chloropropyl)-8-chloro-6-hydroxyoctylamine (120476-67-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: LiOH*H2O / aq. ethanol / Ambient temperature 2: 89 percent / N-methylmorpholine, 1-N-hydroxybenzotriazole, dicyclohexylcarbodiimide / dimethylformamide / 96 h / Ambient temperature 3: 75.4 percent / B2H6 / tetrahydrofuran / Ambient temperature View Scheme

6-hydroxy-8-chlorooctanoic acid ethyl ester (1070-65-1) → N-(3-chloropropyl)-8-chloro-6-hydroxyoctanamide (120476-66-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: LiOH*H2O / aq. ethanol / Ambient temperature 2: 89 percent / N-methylmorpholine, 1-N-hydroxybenzotriazole, dicyclohexylcarbodiimide / dimethylformamide / 96 h / Ambient temperature View Scheme

6-hydroxy-8-chlorooctanoic acid ethyl ester (1070-65-1) → N-(tert-butyloxycarbonyl)-N-(3-chloropropyl)-8-chloro-6-hydroxyoctylamine (120476-68-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: LiOH*H2O / aq. ethanol / Ambient temperature 2: 89 percent / N-methylmorpholine, 1-N-hydroxybenzotriazole, dicyclohexylcarbodiimide / dimethylformamide / 96 h / Ambient temperature 3: 75.4 percent / B2H6 / tetrahydrofuran / Ambient temperature 4: 77 percent / NaHCO3, NaCl / CHCl3; H2O / 2 h / Heating View Scheme

6-hydroxy-8-chlorooctanoic acid ethyl ester (1070-65-1) → (8-Chloro-6-hydroxy-octyl)-(3-chloro-propyl)-carbamic acid benzyl ester (120476-75-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: LiOH*H2O / aq. ethanol / Ambient temperature 2: 89 percent / N-methylmorpholine, 1-N-hydroxybenzotriazole, dicyclohexylcarbodiimide / dimethylformamide / 96 h / Ambient temperature 3: 75.4 percent / B2H6 / tetrahydrofuran / Ambient temperature 4: 84 percent / 1M KOH / diethyl ether / Ambient temperature View Scheme

6-hydroxy-8-chlorooctanoic acid ethyl ester (1070-65-1) → N-(tert-butyloxycarbonyl)-N-(3-azidopropyl)-8-azido-6-hydroxyoctylamine (120476-69-9)

Conditions

Yield

Multi-step reaction with 5 steps 1: LiOH*H2O / aq. ethanol / Ambient temperature 2: 89 percent / N-methylmorpholine, 1-N-hydroxybenzotriazole, dicyclohexylcarbodiimide / dimethylformamide / 96 h / Ambient temperature 3: 75.4 percent / B2H6 / tetrahydrofuran / Ambient temperature 4: 77 percent / NaHCO3, NaCl / CHCl3; H2O / 2 h / Heating 5: 93 percent / LiN3, LiI / dimethylformamide / 30 h / 60 °C View Scheme

6-hydroxy-8-chlorooctanoic acid ethyl ester (1070-65-1) → (8-Chloro-6-hydroxy-octyl)-(3-chloro-propyl)-carbamic acid 4-nitro-benzyl ester (120476-76-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: LiOH*H2O / aq. ethanol / Ambient temperature 2: 89 percent / N-methylmorpholine, 1-N-hydroxybenzotriazole, dicyclohexylcarbodiimide / dimethylformamide / 96 h / Ambient temperature 3: 75.4 percent / B2H6 / tetrahydrofuran / Ambient temperature 4: 70 percent / 1M KOH / diethyl ether / Ambient temperature View Scheme

6-hydroxy-8-chlorooctanoic acid ethyl ester (1070-65-1) → (8-Azido-6-hydroxy-octyl)-(3-azido-propyl)-carbamic acid benzyl ester (120476-77-9)

Conditions

Yield

Multi-step reaction with 5 steps 1: LiOH*H2O / aq. ethanol / Ambient temperature 2: 89 percent / N-methylmorpholine, 1-N-hydroxybenzotriazole, dicyclohexylcarbodiimide / dimethylformamide / 96 h / Ambient temperature 3: 75.4 percent / B2H6 / tetrahydrofuran / Ambient temperature 4: 84 percent / 1M KOH / diethyl ether / Ambient temperature 5: 65 percent / LiN3, LiI / dimethylformamide / 30 h / 60 °C View Scheme

6-hydroxy-8-chlorooctanoic acid ethyl ester (1070-65-1) → Methanesulfonic acid 1-(2-azido-ethyl)-6-[(3-azido-propyl)-tert-butoxycarbonyl-amino]-hexyl ester (120476-79-1)

Conditions

Yield

Multi-step reaction with 6 steps 1: LiOH*H2O / aq. ethanol / Ambient temperature 2: 89 percent / N-methylmorpholine, 1-N-hydroxybenzotriazole, dicyclohexylcarbodiimide / dimethylformamide / 96 h / Ambient temperature 3: 75.4 percent / B2H6 / tetrahydrofuran / Ambient temperature 4: 77 percent / NaHCO3, NaCl / CHCl3; H2O / 2 h / Heating 5: 93 percent / LiN3, LiI / dimethylformamide / 30 h / 60 °C 6: 92 percent / Et3N / CH2Cl2 / Ambient temperature View Scheme

6-hydroxy-8-chlorooctanoic acid ethyl ester (1070-65-1) → (8-Azido-6-hydroxy-octyl)-(3-azido-propyl)-carbamic acid 4-nitro-benzyl ester (120476-78-0)

Conditions

Yield

Multi-step reaction with 5 steps 1: LiOH*H2O / aq. ethanol / Ambient temperature 2: 89 percent / N-methylmorpholine, 1-N-hydroxybenzotriazole, dicyclohexylcarbodiimide / dimethylformamide / 96 h / Ambient temperature 3: 75.4 percent / B2H6 / tetrahydrofuran / Ambient temperature 4: 70 percent / 1M KOH / diethyl ether / Ambient temperature 5: 88 percent / LiN3, LiI / dimethylformamide / 30 h / 60 °C View Scheme

6-hydroxy-8-chlorooctanoic acid ethyl ester (1070-65-1) → N1-(3-Amino-propyl)-6-[(3aS,4S,6R,6aR)-6-(6-amino-purin-9-yl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethylsulfanyl]-octane-1,8-diamine

Conditions

Yield

Multi-step reaction with 8 steps 1: LiOH*H2O / aq. ethanol / Ambient temperature 2: 89 percent / N-methylmorpholine, 1-N-hydroxybenzotriazole, dicyclohexylcarbodiimide / dimethylformamide / 96 h / Ambient temperature 3: 75.4 percent / B2H6 / tetrahydrofuran / Ambient temperature 4: 70 percent / 1M KOH / diethyl ether / Ambient temperature 5: 88 percent / LiN3, LiI / dimethylformamide / 30 h / 60 °C 6: 99 percent / Et3N / CH2Cl2 / Ambient temperature 7: 43 percent / sodium methoxide / a) r.t., 48 h, b) 25 deg C, 12 h, sonication 8: 49 mg / H2, ethanol / 10percent Pd/C / methanol / 2585.7 Torr View Scheme

6-hydroxy-8-chlorooctanoic acid ethyl ester (1070-65-1) → Methanesulfonic acid 1-(2-azido-ethyl)-6-[(3-azido-propyl)-benzyloxycarbonyl-amino]-hexyl ester (120496-27-7)

Conditions

Yield

Multi-step reaction with 6 steps 1: LiOH*H2O / aq. ethanol / Ambient temperature 2: 89 percent / N-methylmorpholine, 1-N-hydroxybenzotriazole, dicyclohexylcarbodiimide / dimethylformamide / 96 h / Ambient temperature 3: 75.4 percent / B2H6 / tetrahydrofuran / Ambient temperature 4: 84 percent / 1M KOH / diethyl ether / Ambient temperature 5: 65 percent / LiN3, LiI / dimethylformamide / 30 h / 60 °C 6: 88 percent / Et3N / CH2Cl2 / Ambient temperature View Scheme

6-hydroxy-8-chlorooctanoic acid ethyl ester (1070-65-1) → Methanesulfonic acid 1-(2-azido-ethyl)-6-[(3-azido-propyl)-(4-nitro-benzyloxycarbonyl)-amino]-hexyl ester (120476-80-4)

Conditions

Yield

Multi-step reaction with 6 steps 1: LiOH*H2O / aq. ethanol / Ambient temperature 2: 89 percent / N-methylmorpholine, 1-N-hydroxybenzotriazole, dicyclohexylcarbodiimide / dimethylformamide / 96 h / Ambient temperature 3: 75.4 percent / B2H6 / tetrahydrofuran / Ambient temperature 4: 70 percent / 1M KOH / diethyl ether / Ambient temperature 5: 88 percent / LiN3, LiI / dimethylformamide / 30 h / 60 °C 6: 99 percent / Et3N / CH2Cl2 / Ambient temperature View Scheme

6-hydroxy-8-chlorooctanoic acid ethyl ester (1070-65-1) → {6-[(3aS,4S,6R,6aR)-6-(6-Amino-purin-9-yl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethylsulfanyl]-8-azido-octyl}-(3-azido-propyl)-carbamic acid tert-butyl ester

Conditions

Yield

Multi-step reaction with 7 steps 1: LiOH*H2O / aq. ethanol / Ambient temperature 2: 89 percent / N-methylmorpholine, 1-N-hydroxybenzotriazole, dicyclohexylcarbodiimide / dimethylformamide / 96 h / Ambient temperature 3: 75.4 percent / B2H6 / tetrahydrofuran / Ambient temperature 4: 77 percent / NaHCO3, NaCl / CHCl3; H2O / 2 h / Heating 5: 93 percent / LiN3, LiI / dimethylformamide / 30 h / 60 °C 6: 92 percent / Et3N / CH2Cl2 / Ambient temperature 7: 28 percent / sodium methoxide / a) r.t., 48 h, b) 25 deg C, 12 h, sonication View Scheme

6-hydroxy-8-chlorooctanoic acid ethyl ester (1070-65-1) → {6-[(3aS,4S,6R,6aR)-6-(6-Amino-purin-9-yl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethylsulfanyl]-8-azido-octyl}-(3-azido-propyl)-carbamic acid benzyl ester

Conditions

Yield

Multi-step reaction with 7 steps 1: LiOH*H2O / aq. ethanol / Ambient temperature 2: 89 percent / N-methylmorpholine, 1-N-hydroxybenzotriazole, dicyclohexylcarbodiimide / dimethylformamide / 96 h / Ambient temperature 3: 75.4 percent / B2H6 / tetrahydrofuran / Ambient temperature 4: 84 percent / 1M KOH / diethyl ether / Ambient temperature 5: 65 percent / LiN3, LiI / dimethylformamide / 30 h / 60 °C 6: 88 percent / Et3N / CH2Cl2 / Ambient temperature 7: 80 percent / sodium methoxide / a) r.t., 48 h, b) 25 deg C, 12 h, sonication View Scheme

6-hydroxy-8-chlorooctanoic acid ethyl ester (1070-65-1) → S-(5'-deoxy-5'-adenosyl)-N-(3-aminopropyl)-8-amino-6-thiooctylamine formate salt

Conditions

Yield

Multi-step reaction with 9 steps 1: LiOH*H2O / aq. ethanol / Ambient temperature 2: 89 percent / N-methylmorpholine, 1-N-hydroxybenzotriazole, dicyclohexylcarbodiimide / dimethylformamide / 96 h / Ambient temperature 3: 75.4 percent / B2H6 / tetrahydrofuran / Ambient temperature 4: 70 percent / 1M KOH / diethyl ether / Ambient temperature 5: 88 percent / LiN3, LiI / dimethylformamide / 30 h / 60 °C 6: 99 percent / Et3N / CH2Cl2 / Ambient temperature 7: 43 percent / sodium methoxide / a) r.t., 48 h, b) 25 deg C, 12 h, sonication 8: 49 mg / H2, ethanol / 10percent Pd/C / methanol / 2585.7 Torr 9: 88percent formic acid / 3 h / Ambient temperature View Scheme

6-hydroxy-8-chlorooctanoic acid ethyl ester (1070-65-1) → {6-[(3aS,4S,6R,6aR)-6-(6-Amino-purin-9-yl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethylsulfanyl]-8-azido-octyl}-(3-azido-propyl)-carbamic acid 4-nitro-benzyl ester (120476-70-2)

Conditions

Yield

Multi-step reaction with 7 steps 1: LiOH*H2O / aq. ethanol / Ambient temperature 2: 89 percent / N-methylmorpholine, 1-N-hydroxybenzotriazole, dicyclohexylcarbodiimide / dimethylformamide / 96 h / Ambient temperature 3: 75.4 percent / B2H6 / tetrahydrofuran / Ambient temperature 4: 70 percent / 1M KOH / diethyl ether / Ambient temperature 5: 88 percent / LiN3, LiI / dimethylformamide / 30 h / 60 °C 6: 99 percent / Et3N / CH2Cl2 / Ambient temperature 7: 43 percent / sodium methoxide / a) r.t., 48 h, b) 25 deg C, 12 h, sonication View Scheme

vinyl propionate (105-38-4) + 6-hydroxy-8-chlorooctanoic acid ethyl ester (1070-65-1) → C13H23ClO4 + ethyl (R)-8-chloro-6-hydroxyoctanoate (852383-82-5) + acetaldehyde (75-07-0)

Conditions	Yield
With Novozym 435 (lipase B from Candida antarctica) In di-isopropyl ether at 40℃; for 7h; Resolution of racemate; Enzymatic reaction;	A n/a B n/a C n/a

vinyl n-butyrate (123-20-6) + 6-hydroxy-8-chlorooctanoic acid ethyl ester (1070-65-1) → C14H25ClO4 + ethyl (R)-8-chloro-6-hydroxyoctanoate (852383-82-5) + acetaldehyde (75-07-0)

Conditions	Yield
With Novozym 435 (lipase B from Candida antarctica) In di-isopropyl ether at 40℃; for 7h; Resolution of racemate; Enzymatic reaction;	A n/a B n/a C n/a

6-hydroxy-8-chlorooctanoic acid ethyl ester (1070-65-1) + acetic anhydride (108-24-7) → C12H21ClO4 + ethyl (R)-8-chloro-6-hydroxyoctanoate (852383-82-5)

Conditions	Yield
With Novozym 435 (lipase B from Candida antarctica) In di-isopropyl ether at 40℃; for 7h; Resolution of racemate; Enzymatic reaction;	A n/a B n/a

butanoic acid anhydride (106-31-0) + 6-hydroxy-8-chlorooctanoic acid ethyl ester (1070-65-1) → C14H25ClO4 + ethyl (R)-8-chloro-6-hydroxyoctanoate (852383-82-5)

Conditions	Yield
With Novozym 435 (lipase B from Candida antarctica) In di-isopropyl ether at 40℃; for 7h; Resolution of racemate; Enzymatic reaction;	A n/a B n/a

6-hydroxy-8-chlorooctanoic acid ethyl ester (1070-65-1) + 2-Methylpropionic anhydride (97-72-3) → C14H25ClO4 + ethyl (R)-8-chloro-6-hydroxyoctanoate (852383-82-5)

Conditions	Yield
With Novozym 435 (lipase B from Candida antarctica) In di-isopropyl ether at 40℃; for 7h; Resolution of racemate; Enzymatic reaction;	A n/a B n/a

pentanoic anhydride (2082-59-9) + 6-hydroxy-8-chlorooctanoic acid ethyl ester (1070-65-1) → C15H27ClO4 + ethyl (R)-8-chloro-6-hydroxyoctanoate (852383-82-5)

Conditions	Yield
With Novozym 435 (lipase B from Candida antarctica) In di-isopropyl ether at 40℃; for 7h; Resolution of racemate; Enzymatic reaction;	A n/a B n/a

vinyl acetate (108-05-4) + 6-hydroxy-8-chlorooctanoic acid ethyl ester (1070-65-1) → C12H21ClO4 + ethyl (R)-8-chloro-6-hydroxyoctanoate (852383-82-5) + acetaldehyde (75-07-0)

Conditions	Yield
With Novozym 435 (lipase B from Candida antarctica) In di-isopropyl ether at 40℃; for 7h; Reagent/catalyst; Solvent; Time; Temperature; Resolution of racemate; Enzymatic reaction;	A n/a B n/a C n/a

Upstream product

• 626-86-8 adipinic acid monoethyl ester 

Downstream Products

• 1070-64-0 6,8-dichlorooctanoic acid ethyl ester 
• 120476-75-7 (8-Chloro-6-hydroxy-octyl)-(3-chloro-propyl)-carbamic acid benzyl ester 
• 120476-76-8 (8-Chloro-6-hydroxy-octyl)-(3-chloro-propyl)-carbamic acid 4-nitro-benzyl ester 
• 120476-77-9 (8-Azido-6-hydroxy-octyl)-(3-azido-propyl)-carbamic acid benzyl ester 
• 120476-78-0 (8-Azido-6-hydroxy-octyl)-(3-azido-propyl)-carbamic acid 4-nitro-benzyl ester 
• 120496-27-7 Methanesulfonic acid 1-(2-azido-ethyl)-6-[(3-azido-propyl)-benzyloxycarbonyl-amino]-hexyl ester 
• 120476-80-4 Methanesulfonic acid 1-(2-azido-ethyl)-6-[(3-azido-propyl)-(4-nitro-benzyloxycarbonyl)-amino]-hexyl ester 
• 120476-70-2 {6-[(3aS,4S,6R,6aR)-6-(6-Amino-purin-9-yl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethylsulfanyl]-8-azido-octyl}-(3-azido-propyl)-carbamic acid 4-nitro-benzyl ester 
• 852383-82-5 ethyl (R)-8-chloro-6-hydroxyoctanoate 
• 75-07-0 acetaldehyde 

Relevant academic research and scientific papers

6-hydroxy-8-chloro ethyl caprylate preparation method thereof

The present invention discloses a preparation method of a lipoic acid key intermediate 6-hydroxy-8-chloro ethyl caprylate having a structure formula represented by a formula (I), wherein 6-oxo-8-chloro ethyl caprylate having a structure represented by a formula (II) is adopted as a starting raw material and is reduced to prepare the 6-hydroxy-8-chloro ethyl caprylate. Compared to the preparation method in the prior art, the preparation method of the present invention mainly has the following advantages that the synthesis steps are simple, the use of the organic solvent is reduced, the direction discharging of the wastewater is avoided, the generated sodium metaborate is easily separated and cannot react with other substances, the sodium metaborate solid is successfully recovered, and the ammonia water is recovered and utilized; particularly by recovering the sodium metaborate, the possibility is created for the recycling of the boron element through the sodium borohydride preparation with the further industrial recovery of the boron element; and the whole process meets the green synthesis and cleaning production technology requirement, and is suitable for the large-scale industrial production. The formulas (I) and (II) are defined in the specification.