A solution of potassium tert-butoxide (1 M in THF, 1.55 mL, 1.55 mmol) was added dropwise to a 0° C. solution of tert-butyl (4S,7S,10aS)-7-(hydroxymethyl)-5-oxooctahydro-2H-pyrido[2,1-b][1,3]thiazepin-4-ylcarbamate (513 mg, 1.55 mmol) in THF (5 mL). The reaction mixture turned yellow in color. After 15 min of stirring, iodomethane (441 mg, 3.10 mmol) was added. The ice bath was removed and the reaction mixture was stirred at rt overnight. Water was added to the reaction and the mixture was concentrated to remove most of the THF. The aqueous solution was then extracted with EtOAc. The organic phase was isolated, washed with saturated aqueous NaCl, dried over MgSO4, filtered and concentrated. The crude product was purified using silica gel chromatography (ISCO system) eluting with a gradient of 0-60% EtOAc/Hex to give tert-butyl (4S,7S,10aS)-7-(methoxymethyl)-5-oxooctahydro-2H-pyrido[2,1-b][1,3]thiazepin-4-ylcarbamate (83 mg, 0.24 mmol, 16% yield) as a colorless oil. Anal. Calcd. for C16H28N2O4S m/z 344.4. found: 345.1 (M+H)+.
