Trifluoroacetic acid → 4-[(R)-4-(3-Chloro-4-trifluoromethyl-phenyl)-3-methyl-7-oxo-2,3,4,7-tetrahydro-[1,4]diazepin-1-yl]-butyric acid

Participants

Reaction Steps

A cooled solution (0° C.) of 1.00 g (2.00 mmol) of 4-[[(R)-2-(3-chloro-4-trifluoromethyl-phenylamino)-propyl]-(3,3-dimethoxy-propionyl)-amino]-butyric acid tert-butyl ester (22% ee) in 18 ml CH2Cl2 was treated with 2.25 ml (29.40 mmol) of trifluoroacetic acid and after 2 h at RT with 1.55 ml (9.80 mmol) of triethylsilane. The reaction was stirred at RT for 16 h, cooled (0° C.) and neutralized with 4.09 ml (29.40 mmol) of triethylamine. The residue was dissolved in diethyl ether and cold water. The reaction was extracted with 10% aq. KHSO4 solution/EtOAc (3×). The organic phases were washed with 10% aq. KHSO4 solution, dried over Na2SO4 and evaporated. Flash silica gel column (CH2Cl2/MeOH 99:2 to 9:1) afforded 0.57 g (74%) of the title compound as a 61:39 mixture of the (R) and (S) diastereomers as brown oil. MS: 389.09 (M−H−, Cl).

Provenance & Evidence