Dichloroacetyl chloride → (R)-tert-butyl 4-(tert-butoxycarbonylamino)-7-(2,2-dichloro-N-(2-(3-(2,6-dichlorophenyl)isoxazol-5-yl)pyridin-4-yl)acetamido)-5-oxoheptanoate

Participants

Reaction Steps

(R)-tert-butyl 4-(tert-butoxycarbonylamino)-7-(2-(3-(2,6-dichlorophenyl)isoxazol-5-yl)pyridin-4-ylamino)-5-oxoheptanoate (280 mg, 0.45 mmol) was dissolved in anhydrous dichloromethane with triethylamine (126 μL, 0.90 mmol). The mixture was cooled in an ice-bath under nitrogen, then a solution of dichloroacetyl chloride (66 μL, 0.68 mmol) was added dropwise. After the addition was completed the ice-bath was removed and the mixture was stirred at room temperature overnight. The reaction mixture was diluted with dichloromethane and then washed successively with water, 10% hydrochloric acid and saturated sodium bicarbonate solution. The organic solution was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography, on silica gel, eluting with 99:1 dichloromethane:methanol to yield (R)-tert-butyl 4-(tert-butoxycarbonylamino)-7-(2,2-dichloro-N-(2-(3-(2,6-dichlorophenyl)isoxazol-5-yl)pyridin-4-yl)acetamido)-5-oxoheptanoate (165 mg) as a white foam. 1H NMR (CDCl3): 8.77 (m, 1H), 7.89 (m, 1H), 7.42 (m, 2H), 7.40-7.31 (m, 2H), 7.07 (s, 1H), 6.00 (s, 1H), 5.20 (m, 1H), 4.20 (m, 1H), 4.00 (m, 2H), 2.97 (m, 2H), 2.27 (m, 2H), 2.10 (m, 1H), 1.78 (m, 1H), 1.41 ppm (m, 18H). MW=730 confirmed by LC-MS, tr=13.34 min (Method A) MH+=728-732.

Provenance & Evidence