Citric Acid → tert-Butyl(3R)-6-cyclohexyl-3-[3-(hydroxymethyl)-1,2,4-oxadiazol-5-yl]hexanoate

HRID 1279870Notes

Reaction equation

HRID 1279870 reaction equation
[C:1]([O:5][C:6](=[O:28])[CH2:7][C@H:8]([C:18]1[O:22][N:21]=[C:20]([C:23](OCC)=[O:24])[N:19]=1)[CH2:9][CH2:10][CH2:11][CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1)([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(O)C>[CH:12]1([CH2:11][CH2:10][CH2:9][C@@H:8]([C:18]2[O:22][N:21]=[C:20]([CH2:23][OH:24])[N:19]=2)[CH2:7][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:28])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]1

Participants

5

Reactant 3

HCID 311Citric AcidHCID 4311764Sodium borohydrideHCID 59909797ethyl 5-{(1R)-1-[2-(tert-butoxy)-2-oxoethyl]4-cyclohexylbutyl}-1,2,4-oxadiazole-3-carboxylate

Product 1

HCID 59909744tert-Butyl(3R)-6-cyclohexyl-3-[3-(hydroxymethyl)-1,2,4-oxadiazol-5-yl]hexanoateYield 98.7%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of ethyl 5-{(1R)-1-[2-(tert-butoxy)-2-oxoethyl]-4-cyclohexylbutyl)1,2,4-oxadiazole-3-carboxylate (Preparation 3) (15.2 g, 38.50 mmol) in ethanol (120 ml) was treated with portions of sodium borohydride (1.46 g, 38.50 mmol) and the resulting mixture was was stirred at room temperature under a nitrogen atmosphere for 5 hours. Aqueous citric acid (5% w/v solution) was added slowly and the mixture was stirred at room temperature for a further 30 minutes. The organic solvent was removed under reduced pressure. The aqueous layer was diluted with water and extracted with ethyl acetate giving an emulsion. Anhydrous sodium chloride was added to break up the emulsion. The combined organic layers were washed with saturated sodium hydrogen carbonate solution and brine, dried over anhydrous sodium sulphate, filtered and the solvent removed under reduced pressure to afford the title compound as a colourless oil (13.4 g).

Workup

  1. stirringthe mixture was stirred at room temperature for a further 30 minutes
  2. customThe organic solvent was removed under reduced pressure
  3. additionThe aqueous layer was diluted with water
  4. extractionextracted with ethyl acetate giving an emulsion
  5. additionAnhydrous sodium chloride was added
  6. washThe combined organic layers were washed with saturated sodium hydrogen carbonate solution and brine
  7. dry with materialdried over anhydrous sodium sulphate
  8. filtrationfiltered
  9. customthe solvent removed under reduced pressure

Sources & evidence

ORD record
ord-ad918dcedd784d8fa7365d79734566bc
Source dataset
uspto-grants-2002_09
Patent number
US06448278B2

Reaction notes

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