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

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Reaction Steps

Dissolve 3-tert-butoxycarbonyl-7-chloro-6-dimethylcarbamoylthio-2,3,4,5-tetrahydro-1H-benzo[d]azepine (706 mg, 1.84 mmol) in methanol (20 mL). Add potassium hydroxide (3.5 g, 55 mmol) and heat the mixture at reflux for 3h. Cool to ambient temperature. Pour reaction in saturated aqueous NH4Cl solution. Extract three times with EtOAc. Combine organic extracts, dry over Na2SO4 and concentrate in vacuo to obtain crude 3-tert-butoxycarbonyl-7-chloro-6-mercapto-2,3,4,5-tetrahydro-1H-benzo[d]azepine (602 mg, 100%). Dissolve 3-tert-butoxycarbonyl-7-chloro-6mercapto-2,3,4,5-tetrahydro-1H-benzo[d]azepine (282 mg, 0.9 mmol) in acetone (30 mL). Add 4-benzyloxybenzyl chloride (251 mg, 1.08 mmol), potassium carbonate (powder) (373 mg, 2.7 mmol) and potassium iodide (powder) (15 mg, 0.1 mmol) and reflux for 16 h. Cool the reaction to ambient temperature, dilute with acetone, filter and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (1:0 and 17:3) to give 6-(4-benzyloxybenzylthio)-3-tert-butoxycarbonyl-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine (309 mg, 67%). MS (ES+) m/z: 510 (M+H)+.

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