Ammonium Chloride → methyl (1S,4S)-1-(2,2-difluoroethyl)-4-(2,5-dimethyl-1H-pyrrol-1-yl)cyclopent-2-ene-1-carboxylate

Participants

Reaction Steps

A −40° C. solution of 2 M (in Ethylbenzene/THF/Heptane) LDA (36 ml, 72 mmol) in THF (80 ml) was placed in flask with THF (80 ml) was treated with a solution of methyl (1R,4S)-4-(2,5-dimethyl-1H-pyrrol-1-yl)cyclopent-2-ene-1-carboxylate (7.9 g, 36.3 mmol) in THF (17 ml) while keeping the temperature less than −32° C. The reaction was stirred for 30 min and then 2,2-difluoroethyl trifluoromethanesulfonate was added slowly, keeping the temperature <−28° C. The reaction was stirred with cold bath in place and allow to slowly warm. After 4 hours the reaction was poured into NH4Cl solution and extracted twice with ethyl acetate. The combined organics were washed with brine, dried over MgSO4 and concentrated to give a brown oil. The oil was passed through a column of silica gel with 10% ethyl acetate/hexanes to give methyl (1S,4S)-1-(2,2-difluoroethyl)-4-(2,5-dimethyl-1H-pyrrol-1-yl)cyclopent-2-ene-1-carboxylate as a brown oil. (7.5 g, 73%). 1H NMR (400 MHz, CDCl3) δ ppm 6.07-6.04 (1H), 6.02-6.00 (0.25H) 5.98-5.96 (1H), 5.88-5.86 (0.5H), 5.75-5.72 (2.25H), 5.36-5.30 (1H), 3.74 (3H), 2.53-2.41 (2H), 2.39-2.22 (2H), 2.19 (6H)

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