反应详情

To a stirred solution of 1-benzyl-3-(3,4,5-trichloro-phenyl)-3-trifluoromethyl-pyrrolidine (Preparation 38, 4 g, 9.828 mmol) in 1,2-dichloroethane (40 mL) was added 1-chloroethyl chloroformate (1.91 mL, 17.69 mmol) and the resulting reaction mixture was refluxed for 3 hours. After complete consumption of starting material, reaction mixture was concentrated under reduced pressure to afford yellow oily residue, which was dissolved in MeOH (40 mL) and the mixture was refluxed at 2 hours. After complete consumption of starting material, reaction mixture was concentrated in vacuo to afford yellow oil, to which water (50 mL) was added and extracted with hexane (3×50 mL). Aqueous layer was basified using saturated sodium bicarbonate solution and extracted with ethyl acetate (3×50 mL). Combined organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford brown thick oil (5.5 g, crude). Crude compound was purified by column chromatography using 100-200 mesh silica gel. Desired compound was eluted in 4% methanol in dichloromethane to afford product as yellow thick oil (2.9 g, impure). Impure compound was as such for next reaction. (m/z): 317.9 (M+H).

1. customthe resulting reaction mixture
2. temperaturewas refluxed for 3 hours
3. customAfter complete consumption of starting material, reaction mixture
4. concentrationwas concentrated under reduced pressure
5. customto afford yellow oily residue, which
6. temperaturethe mixture was refluxed at 2 hours
7. customAfter complete consumption of starting material, reaction mixture
8. concentrationwas concentrated in vacuo
9. customto afford yellow oil
10. extractionextracted with hexane (3×50 mL)
11. extractionextracted with ethyl acetate (3×50 mL)
12. dry with materialCombined organic layer was dried over anhydrous sodium sulfate
13. concentrationconcentrated under reduced pressure
14. customto afford brown thick oil (5.5 g, crude)
15. customCrude compound was purified by column chromatography
16. washDesired compound was eluted in 4% methanol in dichloromethane