Ethanol → ethyl (S)-(-)-2-fluorooctanoate

HRID 1603314Notes

Reaction equation

HRID 1603314 reaction equation
S(=O)(=O)(O)O.[F:6][C@@H:7]([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[C:8]([OH:10])=[O:9].[CH2:17](O)[CH3:18]>>[F:6][C@@H:7]([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[C:8]([O:10][CH2:17][CH3:18])=[O:9]

Participants

4

Reactant 3

HCID 702EthanolHCID 1118Sulfuric AcidHCID 54295823(S)-2-fluorooctanoic acid

Product 1

HCID 54108055ethyl (S)-(-)-2-fluorooctanoateYield 87%

Procedure

Partial Resolution of of Ethyl 2-fluorooctanoate by Enzyme Catalysed Hydrolysis.-Ethyl 2-fluorooctanoate 65 (71.6 g, 0.377 mol) was added to 0.063M phosphate buffer (pH 7.0) (280 ml) and deionised water (280 ml) in a beaker fitted with a pH electrode, magnetic stirrer bar and a cooling bath. Pseudomonas lipase (Amano PS) (22 mg) was added and the mixture was stirred at ca 5° C. The pH was maintained at ca. 7 by adding 1.0M sodium hydroxide solution via a syringe pump. Hydrolysis continued until 151 ml of the hydroxide solution had been added (40% conversion). The mixture was extracted with ether (3 times) and the combined organic solutions were washed with brine, dried (K2CO3) and evaporated to give partially resolved (R)-ester. The aqueous layer was acidified to pH 2.7 with conc. hydrochloric acid and extracted with ether. The organic solutions were dried and evaporated to give partially resolved (S)-(-)-2-fluorooctanoic acid. Concentrated sulphuric acid (2 ml) was added to (S)-2-fluorooctanoic acid (24.0 g, 0.15 mol) in ethanol (200 ml) and the solution was heated under reflux for 4 h. Most of the ethanol was distilled off at atmospheric pressure; dichloromethane was added and the solution was washed with sat. sodium bicarbonate solution until neutral. brine, dried (MgSO4) and evaporated. The yellow liquid was distilled to give partially resolved ethyl (S)-(-)-2-fluorooctanoate 66 (25.13g, 87%) b.p. 68° C. at 0.45 mm Hg.

Workup

  1. temperaturethe solution was heated
  2. temperatureunder reflux for 4 h
  3. distillationMost of the ethanol was distilled off at atmospheric pressure
  4. additiondichloromethane was added
  5. washthe solution was washed with sat. sodium bicarbonate solution until neutral
  6. dry with materialbrine, dried (MgSO4)
  7. customevaporated
  8. distillationThe yellow liquid was distilled

Sources & evidence

ORD record
ord-816901a88d3849d9b8e8ec0aa9ed7073
Source dataset
uspto-grants-1999_11
Patent number
US05986096

Reaction notes

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