Diisopropylethylamine → tert-Butyl 3-(4-chloro-3-{[4,4,4-trifluoro-3-methyl-2-(4-methylpiperidin-1-yl)butanoyl]amino}phenyl)propanoate

Participants

Reaction Conditions

Reaction Steps

270 mg of 4,4,4-trifluoro-3-methyl-2-(4-methylpiperidin-1-yl)butanoic acid (crude product, racemic diastereomer mixture) were dissolved in 2.5 ml of pyridine and 4.9 ml of DMF, and 286 mg (1.12 mmol) of tert-butyl 3-(3-amino-4-chlorophenyl)propanoate and 527 mg (1.37 mmol) of HATU were added at RT. The mixture was stirred at 40° C. overnight. A further 0.5 eq. of HATU and 2 ml of N,N-diisopropylethylamine were added, and the reaction mixture was once more stirred at 50° C. for 5 h and then added to water. The mixture was extracted three times with ethyl acetate and the combined organic phases were washed with a little 1 N hydrochloric acid, dried over magnesium sulphate and concentrated under reduced pressure. The crude product was purified by preparative RP-HPLC (mobile phase acetonitrile/water). This gave 50 mg of the target product (9.6% of theory) as a diastereomer mixture (about 3:2).

Provenance & Evidence