Tetrahydrofuran → HCID 86673650, compound

Participants

Reaction Steps

(S)-5-Biphenyl-4-ylmethyl-1-((E)styryl)-pyrrolidin-2-one (3a, R1=styryl) (2.0 g, 5.7 mmol) is dissolved in 15 mL of anhydrous tetrahydrofuran, cool to −10˜−15° C. by ice salt bath, add LiHMDS (14.2 mL, 14.2 mmol, 1 M in tetrahydrofuran) dropwise under nitrogen atmosphere, the result mixture is stirred at this temperature for 30 min, then add isobutyryl chloride (820 mg, 6.8 mmol) as a solution in 5 mL of anhydrous tetrahydrofuran dropwise, keep the temperature below −5° C., stir for 1 h, quench with saturated NH4Cl aqueous solution, add 50 mL of ethyl acetate, separate the aqueous phase, wash with saturated Na2CO3 aqueous solution and brine, dry over anhydrous Na2SO4, evaporate the solvent under vacuum to obtain (S)-5-Biphenyl-4-ylmethyl-3-(2,2-dimethyl propionyl)-1-((E)-styryl)-pyrrolidin-2-one (4a, R1=styryl, R4=t-butyl), which is direct used in next step. The ratio of (3S,5S) to (3R,5S) is 80:20 as determined by HPLC. Spectroscopic data as Example 15, Method 1.

Provenance & Evidence