反应详情

HCl salt of (3aS,7aS)-1-piperidin-4-yloctahydro-2H-benzimidazol-2-one (2 g, 7.72 mmol) was dissolved in MeOH (30 mL) and MP carbonate (12 g) was added. The mixture was stirred for one hour at rt and then filtered and concentrated in vacuo to provide a white solid. To a stirred solution of above freebase and tert-butyl 4-oxopiperidine-1-carboxylate (1.8 g, 9.04 mmol) in MeOH (40 mL) was added a solution of sodium cyanoborohydride (1 g, 14.49 mmol) and zinc chloride (0.73 g, 5.36 mmol) in MeOH (20 mL). The resulting solution was stirred at room temperature over night then concentrated in vacuo. A solution of 1N NaOH was added and aqueous phase was extracted several times with dichloromethane. The combined organic phases were washed with brine, dried and then concentrated in vacuo. The residue was purified using flash chromatography (linear gradient starting from 1-12% methanol in dichloromethane) to provide the desired compound as a white solid (2 g, 88%). 1H NMR (400 MHz, CHLOROFORM-D): δ ppm 1.21-1.49 (m, 4H), 1.41 (s, 9H), 1.57-1.67 (m, 1H), 1.66-1.84 (m, 7H), 1.93 (d, J=11.13 Hz, 1H), 2.05-2.32 (m, 5H), 2.29-2.43 (m, 1H), 2.53-2.71 (m, 2H), 2.76-3.05 (m, 4H), 3.56-3.79 (m, 1H), 3.90-4.24 (m, 2H), 4.76 (s, 1H). MS (M+1): 407.3

1. filtrationfiltered
2. concentrationconcentrated in vacuo
3. customto provide a white solid
4. stirringThe resulting solution was stirred at room temperature over night
5. concentrationthen concentrated in vacuo
6. additionA solution of 1N NaOH was added
7. extractionaqueous phase was extracted several times with dichloromethane
8. washThe combined organic phases were washed with brine
9. customdried
10. concentrationconcentrated in vacuo
11. customThe residue was purified