反应详情

1-Benzyloxycarbonylaminocyclohexanecarboxylic acid (5.0 gm, 21.0 mmol) was taken up in DMF (40 mL). The mixture was cooled in an ice bath and then sequentially treated with aminoacetonitrile hydrochloride (3.8 gm, 42 mmol), HATU (8.25 gm, 21 mmol) and triethylamine (8.0 mL, 63 mmol). The reaction was allowed to proceed for 4 hours and then the mixture was concentrated under vacuum. The residue was treated with saturated NaHCO3 solution (40 mL) and ethyl acetate (150 mL). The organic layer was separated, sequentially washed with water, 1 M hydrochloric acid (20 mL), water and brine and dried over anhydrous MgSO4 and concentrated under reduced pressure. The free base of the product was purified from the residue using a plug of silica with ethyl acetate as an eluant. The free base of the product was taken up in dichlormethane (20 ml) and methanesulfonic acid (3.0 eq) and the mixture stirred for approximately 12 hours. The mixture was concentrated and the residue was triturated with ether (100 ml) and dried under vacuum to provide 1-amino-N-cyanomethylcyclohexanecarboxamide methanesulfonic acid salt (5.5 gm, 100% yield). LC-MS: 182.2, M+H+.

1. temperatureThe mixture was cooled in an ice bath
2. concentrationthe mixture was concentrated under vacuum
3. additionThe residue was treated with saturated NaHCO3 solution (40 mL) and ethyl acetate (150 mL)
4. customThe organic layer was separated
5. washsequentially washed with water, 1 M hydrochloric acid (20 mL), water and brine
6. dry with materialdried over anhydrous MgSO4
7. concentrationconcentrated under reduced pressure
8. customThe free base of the product was purified from the residue
9. concentrationThe mixture was concentrated
10. customthe residue was triturated with ether (100 ml)
11. customdried under vacuum