Tetrahydrofuran → HCID 86673650, compound

Participants

Reaction Conditions

Reaction Steps

Under N2, LHMDS (12.5 mL, 1.0 M in tetrahydrofuran, 12.5 mmol) is added to the mixture of (S)-2-Biphenyl-4-ylmethyl-5-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester (3a, R1=t-butoxycarbonyl) (1.76 g, 5 mmol) in 15 mL dry tetrahydrofuran is added to the reaction mixture at −10° C., the resulting mixture is then stirred for 30 min at −10° C. 2,2-dimethyl-propionyl chloride (0.72 g, 6 mmol) is added to the reaction mixture at −10° C., after about 1 hour at −10° C., the reaction mixture is diluted with 10 mL saturated aqueous ammonium chloride solution and stirred for 15 min, stop stirring, and remove the lower aqueous layer. the organic phase is then concentrated in vacuo. Ethyl acetate 20 mL is added, filtered and the filtrate concentrated to give (R/S)-3-(2,2-dimethyl-propionyl)-(S)-5-biphenyl-4-ylmethyl-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester (4a, R1=t-butoxycarbonyl, R4=isopropyl), the ration of (3S,5S) to (3R,5S) is 80:20 as determined by HPLC. 1HNMR (400 MHz, CDCl3): 0.98 (s, 9H, 3CH3), 1.52 (s, 9H, (CH3)3), 2.19 (m, 1H, 3-CHH), 2.42 (m, 1H, 3CHH), 2.67 (m, 1H, 5-CHH), 2.92 (m, 1H, 5-CHH), 3.09 (m, 1H, 2-CH), 4.38 (m, 1H, 4-CH), 7.10˜7.80 (9H, m, aromatic).

Provenance & Evidence