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

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Reaction Steps

Add sodium hydride (22 mg, 0.54 mmol, 60% dispersion in mineral oil) to phenol (42 mg, 0.04 mL, 0.45 mmol) in anhydrous DMF (2 mL). Stir the mixture under nitrogen for 5 min and then add 3-tert-butoxycarbonyl-7-chloro-6-chloromethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine (175 mg, 0.45 mmol) in anhydrous DMF (2 mL) followed by catalytic potassium iodide (1 mg). Stir the reaction at 45° C. for 12 h then cool to room temperature and partition between EtOAc/water. Wash the organic phase with brine. Dry the organic phase over MgSO4, filter and concentrate in vacuo to give a yellow oil. Purify the crude mixture by chromatography on silica gel eluting with hexane/EtOAc (9:1) to give 3-tert-butoxycarbonyl-7-chloro-6-phenoxymethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine as a colorless oil (59 mg, 36%).

Provenance & Evidence