Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → tert-butyl 1-[(4-chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}phenyl)(hydroxy)methyl]cyclopropanecarboxylate

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Reaction Steps

A solution of 2.65 g (9.92 mmol) of (2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoic acid, 1.97 g (6.62 mmol) of tert-butyl 1-[(3-amino-4-chlorophenyl)(hydroxy)methyl]cyclopropane-carboxylate and 3.27 g (8.60 mmol) of 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) in 5 ml of pyridine and 10 ml of DMF was stirred at room temperature for three days. 100 ml of ethyl acetate were then added to the mixture, and the solution obtained was washed with 1 M hydrochloric acid and saturated sodium chloride solution. The solution was dried over magnesium sulphate and then filtered, and the filtrate was evaporated to dryness. The crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 50:1→40:1→30:1). The product obtained in this manner was taken up in 100 ml of ethyl acetate, and the solution was extracted three times with saturated sodium bicarbonate solution. The organic phase was washed once more with saturated sodium chloride solution, then dried over magnesium sulphate and finally concentrated to dryness under reduced pressure. This gave 2.75 g of the target compound (76% of theory).

Provenance & Evidence