反应详情

To a solution of (R)-tert-butyl-4,4-difluoro-2-(3-fluorophenyl)pyrrolidine-1-carboxylate (I-8) (0.9 g, 3.0 mmol) in DCM (20 mL) was added TFA (2 mL, 27 mmol) and stirred at room temperature for 2 hours. The reaction was cooled to 0° C. and aqueous NaHCO3 was added while rapidly stirring. The organic phase was separated and washed with aqueous NaHCO3, dried over anhydrous sodium sulfate, filtered and reduced to dryness to yield (R)-4,4-difluoro-2-(3-fluorophenyl)pyrrolidine (I-9) as a light yellow oil that crystallizes on standing. 1H NMR (400 MHz, CD3OD) δ 7.40 (q, J=8.0 Hz, 1 H), 7.23 (d, J=8.8 Hz, 1 H), 7.20 (d, J=10.0 Hz, 1 H), 7.05 (dt, J=8.8, 2.4 Hz, 1 H), 4.41 (dd, J=10.4, 7.2 Hz, 1 H), 3.48 (q, J=12.0 Hz, 1 H), 3.30 (q, J=15.2 Hz, 1 H), 2.74-2.63 (m, 1 H), 2.29-2.14 (m, 1 H). MS m/z 202.1 (M+1)+.

1. temperatureThe reaction was cooled to 0° C.
2. stirringwhile rapidly stirring
3. customThe organic phase was separated
4. washwashed with aqueous NaHCO3
5. dry with materialdried over anhydrous sodium sulfate
6. filtrationfiltered