2-Aminothiophenol → 3-(2-chloro-phenyl)-3,4-dihydro-2H-1,4-benzothiazine

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Reaction Steps

2-[3-(2-Chloro-phenyl)-3,4-dihydro-2H-1,4-benzothiazin-7-yl]-1,1,1,3,3,3-hexafluoro-propan-2-ol: To 2-amino-benzenethiol (1.07 mL, 10 mmol) in DMF (10 mL) under an argon atmosphere was added o-bromo-2-chloro-acetophenone (1.5 mL, 9.8 mmol) at 0° C. and the reaction was warmed to rt. After 10 min, NaBH3CN (1.5 g, 71 mmol) was added portion-wise over 5 min and the reaction was stirred for 16 h. The reaction was quenched with 1N HCl, then neutralized to pH 8 with conc. NaHCO3. The product was extracted with ether, washed with water, dried over MgSO4, and concentrated. The resulting residue was purified by flash chromatography to give 3-(2-chloro-phenyl)-3,4-dihydro-2H-1,4-benzothiazine (1.7 g). A mixture of this intermediate (420 mg, 1.6 mmol) and hexafluoroacetone: 1.5 H2O (620 mg, 3.2 mmol) in DCM (1 mL) was heated in a sealed tube in a microwave reactor at 160° C. for 80 min. The resulting mixture was purified by flash chromatography to give 200A (260 mg). LC/MS m/z 427.87 (M+H)+. 1H NMR (400 MHz, CDCl3) δ ppm 3.03-3.15 (m, 2H) 5.26 (m, 1H) 6.58 (d, J=8, 1H) 7.24-7.28 (m, 2H) 7.37-7.43 (m, 2H).

Provenance & Evidence