2,6-Lutidine → Benzyl (2S)-3-cyclobutyl-2-hydroxypropanoate

Participants

Reaction Steps

A solution of 1.84 g (7.8 mmol) of 2-(S)-hydroxy-3-(cyclobutyl)propionic acid, benzyl ester (Hydroxy Ester 2) in 30 mL of CH2Cl2 at −5° C. was treated with 1.40 mL (8.4 mmol) of trifluoromethanesulfonic anhydride maintaining the internal temperature at less than 0° C. The resulting mixture was stirred cold for 2 min, then treated with 1.10 mL (9.6 mmol) of 2,6-lutidene, maintaining the internal temperature at less than 0° C. The resulting mixture was stirred cold for 30 min, then treated with a solution of 2.65 g (9.5 mmol) of 3-(R)-(t-butyldimethylsilyloxymethyl)-4-(S)-phenylpyrrolidine (Pyrroldine 1) in 10 mL of CH2Cl2 and 3.00 mL (31.2 mmol) of DIEA. The resulting mixture was warmed to rt and stirred for 20 h. The reaction was quenched with 50 mL of sat'd NaHCO3 and the quenched mixture was extracted with 200 mL of ether. The ether extract was dried over MgSO4 and concentrated. Flash chromtography on 150 g of silica gel using 20:1 v/v hexanes/ether as the eluant afforded 3.23 g (81 % based on Hydroxy Ester 2) of the title compound: 1H NMR (300 MHz) δ-0.25 (s, 3H), −0.21 (s, 3H), 0.84 (s, 9H), 1.57-2.07 (8H), 2.29-2.39 (2H), 2.66-2.77 (m, 2H), 2.93 (q, J=7.8, 1H), 3.06 (t, J=8.4, 1H), 3.19 (t, J=8.4, 1H), 3.26 (dd, J=2.1, 6.3, 1H), 3.45-3.60 (m, 2H), 5.15 (s, 2H), 7.17-7.38 (1OH).

Provenance & Evidence