反应详情

To a stirred solution of 1-benzyl-3-(3,5-dichloro-4-fluoro-phenyl)-3-trifluoromethyl-pyrrolidine (Preparation 30, 6.1 g, 15.60 mmol) in 1,2-dichloroethane (50 mL) was added 1-chloroethyl chloroformate (3.01 mL, 28.08 mmol) at room temperature. Resulting reaction mixture was refluxed for 3 hours. After complete consumption of starting material, reaction mixture was concentrated in vacuo to afford brown thick oil. Brown thick oil was dissolved in MeOH (50 mL) and refluxed for 2 hours. Progress of reaction was monitored by TLC. After complete consumption of starting material, reaction mixture was again concentrated to afford brown thick oil, to which water was added (100 mL) and washed with hexane (3×50 mL). Aqueous layer was basified by saturated sodium bicarbonate solution, extracted with ethyl acetate (3×50 mL). Combined organic layer was dried over anhydrous sodium sulfate, concentrated under reduced pressure to afford product as brown thick oil (6.1 g, crude). Crude was purified by column chromatography on (100-200 mesh silica). Desired product was eluted in 25% ethyl acetate in hexane to afford brown semi solid (3.8 g, 80.68%). 1H-NMR (400 MHz, DMSO-d6) δ: 2.39-2.46 (m, 1H), 2.53-2.58 (m, 1H), 2.99-3.13 (m, 2H), 3.53 (d, 1H, J=12.84 Hz), 3.65 (d, 1H, J=12.84 Hz), 7.77 (d, 2H J=6.28 Hz). (m/z): 302.2 (M+H).

1. customResulting
2. customreaction mixture
3. temperaturewas refluxed for 3 hours
4. customAfter complete consumption of starting material, reaction mixture
5. concentrationwas concentrated in vacuo
6. customto afford brown thick oil
7. temperaturerefluxed for 2 hours
8. customProgress of reaction
9. customAfter complete consumption of starting material, reaction mixture
10. concentrationwas again concentrated
11. customto afford brown thick oil
12. washwashed with hexane (3×50 mL)
13. extractionextracted with ethyl acetate (3×50 mL)
14. dry with materialCombined organic layer was dried over anhydrous sodium sulfate
15. concentrationconcentrated under reduced pressure