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

Temperature

-78 °C

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).

1. stirringThe reaction mixture was stirred at −78° C. for 1 hr
2. temperaturewas slowly warmed to 0° C. over 20 min
3. washThe organics were washed with saturated aqueous NaHCO3(50 mL), water (100 mL) and saturated aqueous NaCl (50 mL)
4. customThe organic layer was separated
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated
8. customThe residue was purified
9. washeluting with a gradient of 0-50% EtOAc/Hex

ORD record

ord-6aa71428a3a04ea4a1622a6a74246a45

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09346852B2