Water → HCID 86684916, compound

Participants

Reaction Steps

(2S,4S)-4-Hydroxy-1-(1-trifluoromethyl-cyclopropanecarbonyl)-pyrrolidine-2-carboxylic acid (1-cyano-cyclopropyl)-amide (100.0 g, 301.8 mmol) was dissolved in tetrahydrofuran (500 mL). The mixture was cooled to 2° C. (ice bath), benzenesulfonyl chloride (99%, 48 mL, 370.5 mmol), 4-(dimethylamino)pyridine (98%, 2.0 g, 16.0 mmol), and triethylamine (75.0 mL, 539 mmol) were added subsequently and the mixture was stirred for 15 min. The reaction was allowed to warm to room temperature and stirred for 20 h. After cooling to 2° C. (ice bath), water (150 mL) and methanol (350 mL) were added. Tetrahydrofuran was distilled off carefully in vacuo (ca. 500 mL) and water (500 mL) was added slowly. After addition of 300 mL water, crystallization was induced by addition of seed crystals. The resulting suspension was stirred for 30 min at 2° C. (ice bath) and filtered. The solid was washed with methanol/water 1:2 (v/v, 300 mL) and heptane (300 mL) and dried in vacuo to afford the title compound as off-white crystals (140.8 g, 99%). 1H NMR (CDCl3, 400 MHz): δ 1.06-1.27 (m, 4H), 1.28-1.41 (m, 2H), 1.44-1.54 (m, 2H), 2.26 (ddd, J=5.9 Hz, 9.4 Hz, 14.2 Hz, 1H), 2.59 (ddd, J=3.8 Hz, 3.8 Hz, 14.2 Hz, 1H), 3.90 and 4.03 (ABX, JAB=12.5 Hz, JAx=4.0 Hz, JBX=5.2 Hz, each 1H), 4.57 (br d, J=5.1 Hz, 1H), 5.02-5.09 (m, 1H), 7.08 (br s, 1H), 7.61 (t, J=7.8 Hz, 2H), 7.71 (t, J=7.5 Hz, 1H), 7.95 (d, J=7.2 Hz, 2H).

Provenance & Evidence