Potassium Hydroxide → 3-tert-butoxycarbonyl-7-chloro-6-mercapto-2,3,4,5-tetrahydro-1H-benzo[d]azepine

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Reaction Conditions

Reaction Steps

To 3-tert-butoxycarbonyl-7-chloro-6-dimethylcarbamoylthio-2,3,4,5-tetrahydro-1H-benzo[d]azepine (723 mg, 1.88 mmol) in methanol (10 mL) add potassium hydroxide pellets (3.34 g, 60.2 mmol) and stir mixture at 50° C. for 2 h. Cool to ambient temperature, add aqueous saturated ammonium chloride, extract three times with EtOAc, dry over anhydrous Na2SO4, and concentrate in vacuo to give the crude 3-tert-butoxycarbonyl-7-chloro-6-mercapto-2,3,4,5-tetrahydro-1H-benzo[d]azepine. Dissolve the compound in DMF (5 mL), add cesium carbonate (920 mg, 2.82 mmol) and 1-bromomethyl-4-(3,3,3-trifluoro-2-methyl-2-trifluoromethyl-propane-1-sulfinyl)-benzene (824 mg, 2.071 mmol) and stir 2 h at ambient temperature. Dilute with water, extract three times with EtOAc, dry over anhydrous Na2SO4, and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (9:1) to give 3-tert-butoxycarbonyl-7-chloro-6-[4-(3,3,3-trifluoro-2-methyl-2-trifluoromethyl-propane-1-sulfinyl)-benzylthio]-2,3,4,5-tetrahydro-1H-benzo[d]azepine as a yellow oil (986 mg, 83%). Use a method similar to the General Procedure 14 to give the title compound as a white foam. MS (ES+) m/z: 530 (M+H)+.

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