反应详情

温度

-78 °C

1 g (4 mmol) (S)-5-biphenyl-4-ylmethylpyrrolidin-2-one (1-a, R1=H) is dissolved in 10 ml dry THF and cooled to −78° C. After the addition of 2.76 ml butyl lithium in hexane (1.59 M), the yellow solution is stirred at −78° C. for 30 min. Subsequently, 676 l (820 mg, 4.8 mmol) benzyl chloroformate (Cbz-Cl) is added and stirring is continued at −78° C. for 2 h. The reaction is then quenched by addition of 12 ml saturated NH4Cl solution followed by 10 ml water and then extracted with 2×40 ml isopropyl acetate. The layers are separated and the organic layer is dried over MgSO4, filtered and evaporated. The resulting residue (1.73 g) is purified on column chromatography (dichloromethane:methanol=99.5:0.5) to give (S)-2-Biphenyl-4-ylmethyl-5-oxo-pyrrolidine-1-carboxylic acid benzyl ester (1-a, R1=Cbz) as off-white solid. NMR (400 MHz, DMSO-d6, /ppm): 7.66 (m, 2H); 7.60 (m, 2H); 7.51-7.34 (m, 8H); 7.26 (d, J=8.2, 2 H); 5.28 (s, 2H); 4.37 (m, 1H); 3.05 (dd, J=3.3, 13.1, 1H); 2.88 (dd, J=9.0, 13.1, 1H); 2.45 (m, 1H); 2.28 (m, 1H); 2.01 (m, 1H); 1.77 (m, 1H). MS (ESI, m/e) 386 [M+H]+, 788 [2M+NH4+]. IR (solution in CH2Cl2, /cm−1): 3092; 2957; 1756; 1705; 1488; 1396; 1304; 1287; 1231; 1139; 1043; 952; 750.

1. stirringstirring
2. waitis continued at −78° C. for 2 h
3. customThe reaction is then quenched by addition of 12 ml saturated NH4Cl solution
4. extractionextracted with 2×40 ml isopropyl acetate
5. customThe layers are separated
6. dry with materialthe organic layer is dried over MgSO4
7. filtrationfiltered
8. customevaporated
9. customThe resulting residue (1.73 g) is purified on column chromatography (dichloromethane:methanol=99.5:0.5)