Dichloromethane → HCID 86684920, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred suspension of methanesulfonic acid (3S,5S)-5-(1-cyano-cyclopropylcarbamoyl)-1-(1-trifluoromethyl-cyclopropanecarbonyl)-pyrrolidin-3-yl ester (20.5 g, 50 mmol) and 4-(2-methyl-pyridin-4-yl)-2-trifluoromethyl-benzenethiol hydrochloride (17.6 g, 57.5 mmol) in THF (75 mL) was added at 0° C. 25% sodium tert-butoxide in THF (43.2 g, 112.5 mmol) over 30 min and the reaction mixture was stirred at 50° C. for 4.5 h. After cooling to 10° C., the reaction mixture was added to dichloromethane (250 mL) and washed twice with deionized water (2×250 mL). The organic layer was dried (Na2SO4), filtered, and evaporated by rotary evaporation (45° C./≧10 mbar), affording the crude title product (30.9 g, 106%) as a beige, amorphous foam which was used without further purification in the next step. 1H NMR (CDCl3, 400 MHz) δ 1.10-1.35 (m, 6H), 1.47-1.58 (m, 2H), 2.00-2.11 (m, 1H), 2.65 (s, 3H), 2.92-3.01 (m, 1H), 3.92 & 4.02 (ABC, JAB=11.8 Hz, JAC=5.0 Hz, JBC=6.2 Hz, each 1H), 4.17 (quint, J=5.5 Hz, 1H), 4.72 (dd, J1=8.1 Hz, J2=4.8 Hz, 1H), 7.31 (dd, J1=5.1 Hz, J2=1.5 Hz, 1H), 7.37 (s, 1H), 7.62 (s, 1H), 7.66 (d, J=8.3 Hz, 1H), 7.80 (dd, J1=8.1 Hz, J2=1.9 Hz, 1H), 7.93 (d, J=2.1 Hz, 1H), 8.60 (d, J=5.1 Hz, 1H). ESI-MS (m/z) [M+H]+ 583 (40).

Provenance & Evidence