Benzyl Bromide → 2-(S)-Hydroxy-3-(cyclopentyl)propanoic acid, benzyl ester

HRID 1068114Notes

Reaction equation

HRID 1068114 reaction equation
[OH:1][C@@H:2]([CH2:6][CH:7]1[CH2:11][CH2:10][CH2:9][CH2:8]1)[C:3]([OH:5])=[O:4].[CH2:12](Br)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>CN(C=O)C.CCOCC>[OH:1][C@@H:2]([CH2:6][CH:7]1[CH2:11][CH2:10][CH2:9][CH2:8]1)[C:3]([O:5][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:4]

Participants

5

Reactant 2

HCID 7498Benzyl BromideHCID 21341064(S)-a-Hydroxy-cyclopentanepropanoic acid

Product 1

HCID 599246112-(S)-Hydroxy-3-(cyclopentyl)propanoic acid, benzyl ester

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 287 mg (1.81 mmol) of 2-(S)-hydroxy-3-(cyclopentyl)propanoic acid (from Step F) in 8 mL of DMF was treated with 0.38 mL (2.72 mmol) of TEA and 0.33 mL (2.77 mmol) of benzyl bromide and stirred at rt for 22 h. The reaction was diluted with 200 ml of ether and washed with 200 mL of H2O, 200 mL of 2.0 N HCl, 200 mL of 1.0 N NaHCO3, 200 mL of H2O and 200 mL of sat'd NaCl. The organic layer was dried over MgSO4 and concentrated. Flash chromatography on silica gel using 17:3 v/v hexanes/EtOAc afforded 102 mg (22%, 95.5% ee) of the title compound: RF: 0.40 (4:1 v/v hexanes/EtOAc); 1H NMR (300 MHz): δ 1.04-1.17 (m, 2H), 1.46-1.87 (m, 8H), 1.99 (m, 1H), 2.65 (m, 1H), 4.22 (dd, J=7.8, 4.8, 11H), 5.23 (ABq, J=12.3, 2H), 7.32-7.41 (m, 5H). HPLC: Chirapak AS 4.6×250 mm column, 17:3 v/v hexanes/iPrOH, 0.5 mL/min, 220 nm. Retention times: (S)-Enantiomer, 12.2 min; (R)-enantiomer, 15.3 min.

Workup

  1. washwashed with 200 mL of H2O, 200 mL of 2.0 N HCl, 200 mL of 1.0 N NaHCO3, 200 mL of H2O and 200 mL of sat'd NaCl
  2. dry with materialThe organic layer was dried over MgSO4
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-8660547394fc41c1bde766b706d70db7
Source dataset
uspto-grants-2001_06
Patent number
US06248755B1

Reaction notes

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