Hydrochloric Acid → HCID 59003238, compound

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Reaction Steps

Inject titanium isopropoxide (1.1 mL, 3.89 mmol) to a mixture of 8-bromo-9-methyl-5-oxo-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid isopropyl ester (882 mg, 2.59 mmol) and 3,5-bis(trifluoromethyl)benzylamine (866 mg, 2.85 mmol) at room temperature under an atmosphere of nitrogen and stir the solution for 14 h. Add methanol (11.3 mL) and sodium borohydride (245 mg, 6.47 mmol) and stir the mixture under nitrogen at room temperature for 2 h. Add 0.1M NaOH (61 mL), stir for 30 min. Filter through celite and wash the residue with AcOEt. Separate organic layer, extract aqueous with AcOEt. Wash organic layer with brine and dry the organic layers over anhydrous magnesium sulfate. Filter and remove the solvent under reduced pressure. To the former crude in dichloromethane (9.8 mL), add acetic anhydride (0.980 mL, 10.36 mmol) dropwise and pyridine (0.980 mL, 10.36 mmol), stir under nitrogen at room temperature for 14 h. Add 1 M hydrochloric acid and extract with dichloromethane. Dry the organic layer over anhydrous sodium sulfate, filter and remove the solvent under reduced pressure. Purify the residue by flash chromatography, eluting with hexanes/ethyl acetate, to afford the title compound (162 mg, 10% over two steps); MS (ES+): 610 (M+H).

Provenance & Evidence