Water → tert-Butyl 1-[3-({N-[(benzyloxy)carbonyl]-4,4,4-trifluorovalyl}amino)-4-fluorobenzyl]cyclopropanecarboxylate

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Reaction Steps

4.80 g (15.7 mmol) of N-[(benzyloxy)carbonyl]-4,4,4-trifluorovaline (racemic diastereomer mixture) and 5.01 g (18.9 mmol) of tert-butyl 1-(3-amino-4-fluorobenzyl)cyclopropanecarboxylate were dissolved in a mixture of 40 ml of DMF and 10 ml of pyridine, and 6.58 g (17.3 mmol) of HATU were added at RT. The reaction mixture was stirred at RT overnight and then added to water. The mixture was extracted three times with ethyl acetate, and the combined organic phases were then washed successively with sat. sodium bicarbonate solution, 1 N hydrochloric acid and sat. sodium chloride solution, dried over magnesium sulphate and concentrated under reduced pressure. The crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 20:1→10:1). This gave 5.34 g of the target product (61.5% of theory, diastereomer ratio about 2.5:1).

Provenance & Evidence