4-Methyloxybenzyl chloride → 2-(S)-Hydroxy-3-(cyclopropyl)propanoic acid, 4-(methoxy)benzyl ester

Participants

Reaction Steps

A solution of 4.30 g (33 mmol) of 2-(S)-hydroxy-3-(cyclopropyl)propanoic acid (from Step A), 6.40 mL (46 mmol) of TEA and 5.90 mL (44 mmol) of 4-(methoxy)benzyl chloride in 40 mL of DMF was stirred at rt for 2 h. The mixture was partitioned between 500 mL of ether and 300 mL of H2O and the layers were separated. The organic layer was washed with 300 mL of 2.0 N HCl, 300 mL of sat'd NaHCO3, 2×300 mL of H2O, 300 mL of sat'd NaCl, dried over MgSO4 and concentrated. Flash chromatography on 500 g of silica gel using 5:1 v/v hexanes/EtOAc as the eluant afforded 4.30 g (52%, 97.5% ee) of the title compound: RF: 0.20 (4:1 v/v hexanes/EtOAc); 1H NMR (300 MHz): δ 0.01-0.09 (m, 2H), 0.40-0.45 (m, 2H), 0.84 (m, 1H), 1.55-1.67 (m, 2H), 2.82 (br m, 1H), 3.81 (s, 3H), 4.25 (br m, 1H), 5.14 (ABq, J=11.8, 2H), 6.90 (d, J=8.7, 2H), 7.29 (d, J=8.7, 2H). HPLC: Chiracel OB 4.6×250 mm column, 65:35 v/v hexanes/EtOH, 0.5 mL/min, 220 nm. Retention times: (S)-enantiomer, 20.4 min; (R)-enantiomer, 17.3 min.

Provenance & Evidence