Pyridine → tert-butyl(2S,3S)-2-methyl-4-oxo-1-(tetrahydro-2H-pyran-4-carbonyl)-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamate

Participants

Reaction Conditions

Reaction Steps

To a 0° C. solution of tert-butyl(2S,3S)-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamate (prepared as in Example 1, 330 mg, 1.13 mmol) in methylene chloride (10 ml) was added pyridine (277 μl, 3.4 mmol) and tetrahydro-2H-pyran-4-carbonyl chloride (185 mg, 1.25 mmol). It was stirred at 0° C. for one hour and then warmed to room temperature and stirred overnight. After this time another portion of tetrahydro-2H-pyran-4-carbonyl chloride (252 mg, 1.70 mmol) was added and the reaction mixture was stirred at room temperature another 3 h. After this time the reaction mixture was diluted with methylene chloride (30 mL), washed with a saturated aqueous sodium bicarbonate solution (30 mL), and saturate aqueous sodium chloride solution (30 mL), the organic layer was then dried over sodium sulfate, filtered to remove the drying agent, and concentrated in vacuo. The crude material was then purified on an Intelliflash 280 system (12 g silica gel column, 20-65% ethyl acetatehexanes) to afford tert-butyl(2S,3S)-2-methyl-4-oxo-1-(tetrahydro-2H-pyran-4-carbonyl)-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamate (210 mg, 46%) as a white foam: LC-MS m/z 426 [M+Na]+.

Provenance & Evidence