反应详情

Dimethyl 2-(3,5-difluorobenzyl)piperidine-1,4-dicarboxylate (8.459 g, 25.84 mmol) was dissolved in acetonitrile (85 mL) and water (1.7 mL). Lithium bromide (17.95 g, 206.74 mmol) and triethylamine (14.33 mL, 103.37 mmol) were added. The suspension was heated to reflux 1.5 h before water (100 mL) and MTBE (300 mL) were added. The organic phase was extracted with water (×2). The combined water phases were acidified to pH 1 with 3.8 M HCl and extracted with MTBE (×2). The combined organic phases were washed with water, dried with MgSO4, filtered through celite and concentrated. The crude product was redissolved in MTBE and washed with 0.1 M HCl (×2) and water. The organic phase was dried with MgSO4 and concentrated to give 2-(3,5-difluorobenzyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid (6.88 g, 85%). MS m/z 314 (M+H)+

1. temperatureThe suspension was heated
2. additionwere added
3. extractionThe organic phase was extracted with water (×2)
4. extractionextracted with MTBE (×2)
5. washThe combined organic phases were washed with water
6. dry with materialdried with MgSO4
7. filtrationfiltered through celite
8. concentrationconcentrated
9. dissolutionThe crude product was redissolved in MTBE
10. washwashed with 0.1 M HCl (×2) and water
11. dry with materialThe organic phase was dried with MgSO4
12. concentrationconcentrated