反应详情

N-tert-butyloxycarbonyl-4-benzylpiperidine-4-carboxylic acid (3.0 g; 9.0 mmol) was dissolved in methylene chloride (25 ml) and EDAC (1.8 g; 9.0 mmol) and HOAt (1.3 g; 9.0 mmol) was added. The mixture was stirred for 15 min, then methyl amine (33% in ethanol; 2.3 ml; 18 mmol) and DIEA (1.6 ml; 9.0 mmol) was added and the mixture was stirred overnight. Methylene chloride (100 ml) was added and the mixture was washed with a saturated aqueous solution of sodium hydrogen carbonate (50 ml) and a aqueous solution of sodium hydrogensulfate (10%, 50 ml), dried (MgSO4) and evaporated in vacuo. The residue was chromatographed on silica (90 g) using a mixture of aqueous ammonia/ethanol/methylene chloride (1:7:92) as eluent to afford 2.8 g of 4-benzyl-4-methylcarbamoylpiperidine-1-carboxylic acid tert-butyl ester.

1. stirringthe mixture was stirred overnight
2. washthe mixture was washed with a saturated aqueous solution of sodium hydrogen carbonate (50 ml)
3. dry with materiala aqueous solution of sodium hydrogensulfate (10%, 50 ml), dried (MgSO4)
4. customevaporated in vacuo
5. customThe residue was chromatographed on silica (90 g)
6. additiona mixture of aqueous ammonia/ethanol/methylene chloride (1:7:92) as eluent