反应详情

To a THF (30 ml) solution of (S)-1-(tert-butoxycarbonyl)-4,4-difluoropyrrolidine-2-carboxylic acid (3.77 g, 15 mmol) at 0° C., BH3.THF solution (1.0 M in THF, 45 ml) was added dropwise over 20 minutes. The reaction mixture was allowed to warm to room temperature and stirring was continued for a total of 16 hours. Reaction went to completion as monitored by LC-MS. The reaction mixture was quenched by the addition of saturated aqueous solution of NaHCO3 (60 ml) at room temperature and the stirring was continued at room temperature for 4 hours. Most THF was removed in vacuo and the mixture was extracted with EtOAc (˜60 ml), two layers were separated, organic layer was washed with brine (˜50 ml), repeat the extraction/wash cycle one more time. Organic layers were combined, dried (Na2SO4), filtered, solvent was removed in vacuo. Crude product was purified by silica gel chromatography (Hexane/EtOAc, gradient from 100:0 to 50:50). Compound (S)-tert-butyl 4,4-difluoro-2-(hydroxymethyl)pyrrolidine-1-carboxylate was obtained as a colorless oil: 2.6473 g (74% yield).

1. customwas continued for a total of 16 hours
2. customReaction
3. customThe reaction mixture was quenched by the addition of saturated aqueous solution of NaHCO3 (60 ml) at room temperature
4. customMost THF was removed in vacuo
5. extractionthe mixture was extracted with EtOAc (˜60 ml), two layers
6. customwere separated
7. washorganic layer was washed with brine (˜50 ml)
8. dry with materialdried (Na2SO4)
9. filtrationfiltered
10. customsolvent was removed in vacuo
11. customCrude product was purified by silica gel chromatography (Hexane/EtOAc, gradient from 100:0 to 50:50)