Trifluoroacetic acid → HCID 68407776, compound

Participants

Reaction Steps

To a solution of tert-butyl [(4-oxocyclohexyl)methyl]carbamate (5.0 g, 22.00 mmol) in dichloromethane (100 ml) was added trifluoroacetic acid (10 ml). The mixture was stirred for 1 h at room temperature, and then concentrated and co-concentrated with toluene (5 ml). A suspension of 4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)benzoic acid (INTERMEDIATE 2, 6.13 g, 20 mmol), o-benzotriazol-1-yl-tetramethyluronium hexafluorophosphate (15.2 g, 40.1 mmol), 1-hydroxybenzotriazole (4.0 g, 29.6 mmol), and diisopropylethylamine (20 ml, 115 mmol) in dichloromethane (100 ml) was stirred for 5 min at room temperature, and then a solution of the deprotected amine in dichloromethane (100 ml) was added. The mixture was stirred overnight at 25° C. The mixture was filtered and then diluted with 300 ml of saturated sodium bicarbonate solution. The phases were separated and the aqueous phase was extracted with 2×100 ml of dichloromethane. The combined organics were washed with 100 ml of brine, dried (sodium sulfate), and concentrated. The residue was purified by flash chromatography on a Biotage Horizon, 65i column, eluting with 1 column volume of 100% dichloromethane followed by a gradient of 0 to 100% ethyl acetate in dichloromethane over 10 column volumes. The resulting product was repurified by flash chromatography on a Biotage Horizon, 65i column, eluting with 1 column volume of 100% hexanes followed by a gradient of 0 to 100% acetone in hexanes over 10 column volumes. The resulting product was crystallized from dichloromethane to provide the title compound (5.52 g, 13.29 mmol, 66.4% yield). Mass spectrum (ESI) 416.0 (M+1).

Provenance & Evidence