4-Methyloxybenzyl chloride → 4-(Methoxy)benzyl 2-(S)-hydroxy-3-(cyclobutyl)propanoate

Participants

Reaction Steps

A mixture of 432 mg (3.0 mmol) of 2-(S)-hydroxy-3-cyclobutyl propanoic acid (from EXAMPLE 19, Step D), 0.61 mL of 4-(methoxy)benzyl chloride and 0.63 mL of TEA was stirred at rt for 20 h. The reaction mixture was partitioned between 100 mL of ether and 50 mL of H2O and the layers were separated. The organic layer was washed with 50 mL of sat'd NaHCO3, 50 mL of 2.0 N HCl, 2×50 mL of H2O and 50 mL of sat'd NaCl, dried over MgSO4 and concentrated. Flash chromatography on 30 g of silica gel using 4:1 v/v hexanes/ether as the eluant afforded 598 mg (75%) of the title compound: 1H NMR (500 MHz) δ 1.56-1.94 (6H), 1.98-2.12 (m, 2H), 2.44-2.56 (m, 1H),2.64 (br s, 1H), 3.82 (s, 3H), 4.11-4.13 (m, 1H), 5.19 (ABq, J=25.0, 2H), 6.90 (d, J=9.0, 2H), 7.30 (d, J=9.0, 2H).

Provenance & Evidence