反应详情

Tetrabutylammonium fluoride (1M solution in THF, 530 mL) was added to (R)-tert-butyl 3-(((methylsulfonyl)oxy)methyl)pyrrolidine-1-carboxylate (30 g from previous step) and the resulting mixture was refluxed overnight. After cooling, the solvent was removed and the residue was partitioned between 10% aqueous citric acid and dichloromethane. The organic layer was washed with water, dried over sodium sulfate, filtered and the solvent was removed on a rotary evaporator. The residue was purified by flash chromatography on a silica gel column (0 to 50% ethyl acetate/hexanes) to afford 14.3 g of (R)-tert-butyl 3-(fluoromethyl)pyrrolidine-1-carboxylate as a yellow oil. 1H NMR (400 MHz, DMSO-d6) δ 4.49-4.41 (m, 1H), 4.37-4.29 (m, 1H), 3.40-3.28 (m, 2H), 3.24-3.18 (m, 1H), 3.02-2.98 (m, 1H), 2.58-2.52 (m, 1H), 1.95-1.88 (m, 1H), 1.67-1.54 (m, 1H), 1.38 (s, 9H).

1. temperaturethe resulting mixture was refluxed overnight
2. temperatureAfter cooling
3. customthe solvent was removed
4. customthe residue was partitioned between 10% aqueous citric acid and dichloromethane
5. washThe organic layer was washed with water
6. dry with materialdried over sodium sulfate
7. filtrationfiltered
8. customthe solvent was removed on a rotary evaporator
9. customThe residue was purified by flash chromatography on a silica gel column (0 to 50% ethyl acetate/hexanes)