3,5-Bis(trifluoromethyl)benzylamine → 5-(3,5-Bis-trifluoromethyl-benzylamino)-8-chloro-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid tert-butyl ester

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Reaction Steps

Add 3,5-bis(trifluoromethyl)benzylamine (3.2 g, 13.1 mmol) followed by titanium isopropoxide (5.0 mL) to 8-Chloro-5-oxo-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid tert-butyl ester (3.5 g, 11.9 mmol) and stir at room temperature overnight. Dilute the mixture with 20 mL of Methanol and add sodium borohydride (23.8 mmol). Stir the suspension at room temperature for 1 h then dilute with water (200 mL) and ethyl acetate (200 mL). Filter the resulting emulsion through celite and wash with ethyl acetate (3×100 mL). Separate the organics and dry over sodium sulfate. Remove the solvent under vacuum and chromatograph the product over silica gel using ethyl acetate/hexane (5-30%) to elute. This affords the title compound (5.7 g, 93%) as an off white solid: MS (ES+): 523 (M+H).

Provenance & Evidence