(2S)-2-PHENYL-4-OXOPYRROLIDINE, N-BOC PROTECTED synthesis

Yield:-

Reaction Conditions:

Stage #1: with oxalyl dichloride;dimethyl sulfoxide in dichloromethane at -78; for 0.166667 h;
Stage #2: tert-butyl (2S,4S)-4-hydroxy-2-phenylpyrrolidine-1-carboxylate in dichloromethane at -78; for 1 h;
Stage #3: with triethylamine in dichloromethane at 0; for 1 h;

Steps:

6.2 Step 2

To a flame dried flask equipped with stir bar was added 150 mL anhydrous dichloromethane which was cooled to -78° C. Oxalyl chloride (3.8 mL, 44 mmol) and DMSO (4.8 mL, 61 mmol) were added sequentially and the reaction stirred for 10 minutes. (2S,4S)-tert-Butyl 4-hydroxy-2-phenylpyrrolidine-1-carboxylate (6-2, 2.28 g, 8.73 mmol) in 10 mL anhydrous dichloromethane was added dropwise and stirred 1 hour at -78° C. Triethylamine (12 mL, 87 mmol) was added and the reaction was warmed to 0° C. over 1 hour. Upon completion, the reaction was washed with 5% NaHCO3, brine and dried over MgSO4. The organic layer was concentrated to provide crude (2S)-tert-butyl 4-oxo-2-phenylpyrrolidine-1-carboxylate (6-3). Recrystallization was effected with EtOAc/hexanes. 1H NMR (300 MHz, CDCl3) δ 7.35 (m, 3H), 7.17 (m, 2H), 5.38 (m, 1H), 4.08 (d, J=19.5 Hz, 1H), 3.90 (d, J=19.3 Hz, 1H), 3.13 (dd, J=18.8, 9.8 Hz, 1H), 2.58 (dd, J=18.6, 2.4 Hz, 1H), 1.40 (br s, 9H); MS 206.0 found, 206.1 (M-C(CH3)3) required.

References:

US2005/38074,2005,A1 Location in patent:Page/Page column 39