Dimethyl Sulfoxide → tert-butyl (4S,7S,10aS)-7-formyl-5-oxooctahydro-2H-pyrido[2,1-b][1,3]thiazepin-4-ylcarbamate

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Reaction Conditions

Reaction Steps

To a round bottom flask was added DCM (10 mL) and a 2 M solution of (COCl)2 in DCM (1.57 mL, 3.14 mmol). The reaction mixture was cooled to −78° C. Then, DMSO (0.445 mL, 6.27 mmol) was slowly added to the reaction mixture over 10 min. The reaction mixture was stirred at −78° C. for 15 min. Then, tert-butyl (4S,7S,10aS)-7-(hydroxymethyl)-5-oxooctahydro-2H-pyrido[2,1-b][1,3]thiazepin-4-ylcarbamate (740 mg, 2.24 mmol) in DCM (5 mL) was added to the reaction mixture over 10 min. The reaction mixture was stirred at −78° C. for 1 hr. Then, TEA (1.37 mL, 9.85 mmol) was added to the reaction, which was slowly warmed to 0° C. over 20 min. The reaction mixture was diluted with DCM (50 mL). The organics were washed with saturated aqueous NaHCO3(50 mL), water (100 mL) and saturated aqueous NaCl (50 mL). The organic layer was separated, dried over MgSO4, filtered and concentrated. The residue was purified using silica gel chromatography (ISCO system) eluting with a gradient of 0-50% EtOAc/Hex to give tert-butyl (4S,7S,10aS)-7-formyl-5-oxooctahydro-2H-pyrido[2,1-b][1,3]thiazepin-4-ylcarbamate (450 mg, 1.37 mmol, 61.2% yield) as a white solid. Anal. Calcd. for C15H24N2O4S m/z 328.4. found: 329.0 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 9.73 (s, 1H), 5.95 (d, J=6.2 Hz, 1H), 5.44-5.21 (m, 1H), 5.02 (d, J=6.0 Hz, 1H), 4.97-4.74 (m, 1H), 3.54-3.24 (m, 1H), 3.06-2.78 (m, 1H), 2.63-2.26 (m, 2H), 2.16-1.75 (m, 3H), 1.52 (d, J=53.2 Hz, 12H).

Provenance & Evidence