Trimethylsilyl iodide → (4S,8S,10aS)-4-amino-8-(trifluoromethyl)hexahydro-2H-pyrido[2,1-b][1,3]thiazepin-5(7H)-one

Participants

Reaction Steps

To a solution of benzyl (4S,8S,10aS)-5-oxo-8-(trifluoromethyl)octahydro-2H-pyrido[2,1-b][1,3]thiazepin-4-ylcarbamate (101 mg, 0.251 mmol) in DCM (1.2 mL) stirred at rt was added iodotrimethylsilane (150 mg, 0.752 mmol) dropwise. After the addition, the resulting yellowish solution was stirred at rt under argon for 2 hr. The reaction mixture was quenched by the dropwise addition of 1 N aqueous HCl, diluted with EtOAc, and extracted with 1 N aqueous HCl (2×3 mL). The combined HCl extracts were washed with EtOAc (2×). The aqueous layer was then basified with 1 N aqueous NaOH solution to pH 9-10 and extracted with DCM (3×10 mL). The combined DCM extracts were washed with water, saturated aqueous NaCl, dried over Na2SO4, filtered and concentrated to give (4S,8S,10aS)-4-amino-8-(trifluoromethyl)hexahydro-2H-pyrido[2,1-b][1,3]thiazepin-5(7H)-one (45 mg, 0.17 mmol, 66% yield) as a white solid. Anal. Calcd. for C10H15F3N2OS m/z 268.2. found: 269.0 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 5.14 (t, J=7.2 Hz, 1H), 4.46 (dd, J=14.7, 2.6 Hz, 1H), 3.88 (dd, J=10.5, 2.8 Hz, 1H), 3.30 (dd, J=14.8, 6.6 Hz, 1H), 3.13 (ddd, J=14.2, 11.0, 2.9 Hz, 1H), 2.74 (ddd, J=14.5, 5.9, 3.1 Hz, 1H), 2.66-2.54 (m, 1H), 2.35-2.23 (m, 1H), 2.18 (ddt, J=14.0, 5.8, 2.9 Hz, 1H), 2.08-1.94 (m, 1H), 1.89-1.55 (m, 5H).

Provenance & Evidence