Triethylamine → HCID 11293464, compound

Participants

Reaction Steps

Titianium(IV) tert-butoxide (0.022 mL, 0.065 mmol, 0.100 equiv) was added to a solution of (1S)-1-cyclopropyl-2-[(2S)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrol-1-yl]-2-oxoethanol (6-2,230 mg, 0.647 mmol, 1 equiv) in dichloromethane (5 mL) at 23° C. followed by triethylamine (0.271 mL, 1.94 mmol, 3.00 equiv) and dimethyl chlorophosphate (0.140 mL, 1.29 mmol, 2.00 equiv). The resulting mixture was stirred for 2 h, then partitioned between saturated sodium bicarbonate solution (50 mL) and ethyl acetate (2×50 mL). The combined organic layers were dried over sodium sulfate and were concentrated. The residue was dissolved in dimethyl sulfide (0.5 mL) and to the resulting solution was added methanesulfonic acid (1 mL). The resulting mixture was stirred for 10 min, then diluted with acetonitrile (3 mL). Purification by reverse-phase LC (H2O/CH3CN gradient w/0.1% TFA present) provided (1S)-1-cyclopropyl-2-[(2S)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrol-1-yl]-2-oxoethyl dihydrogen phosphate (10-1) as a white solid. 1H NMR (500 MHz, CDCl3) major rotamer: δ 7.42-7.04 (m, 8H), 6.46 (s, 1H), 5.95 (m, 1H), 5.14 (br d, 1H, J=14 Hz), 5.04 (br d, 1H, J=14 Hz), 4.46 (t, 1H, J=8.2 Hz), 1.32 (m, 1H), 0.62 (m, 4H). LRMS m/z (M+H) 436.4 found, 436.1 required.

Provenance & Evidence