Methyl iodide → HCID 11341284, compound

Participants

Reaction Conditions

Reaction Steps

In a round bottomed flask, 50 mg (0.0997 mmol) 3-[(3R,4S)-3-({(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}oxy)-4-(4-fluorophenyl)pyrrolidin-1-yl]cyclopent-2-en-1-one (Example 3, step F) was dissolved in tetrahydrofuran (5 mL) under nitrogen atmosphere and cooled to −78° C. To this solution was added by syringe, 0.090 mL (0.9 equiv, 0.0897 mmol) of a 1M solution of LiHMDS in THF. The resulting faint yellow solution was stirred for 1 hr at −78° C. then 0.0155 mL (0.249 mmol) iodomethane was added by syringe. The resulting yellow solution was stirred for 5 min at −78° C. then warmed to RT over 30 min. The reaction was quenched by the addition of 2 mL sat. aq. NH4Cl stirred 5 min then 2 mL water was added. The resulting mixture was extracted with ether (3×10 mL). The combined organic extracts were dried over anhydrous sodium sulfate, filtered and the solvent removed under vacuum to provide a yellow oil. The resulting oil was purified by prep TLC on silica gel eluting with methylene chloride/methanol (9/1). The UV active band with Rf˜0.85 was isolated. The resulting yellow oil (48 mg) was purified by prep HPLC on Chiralcel OD eluting with heptanes/absolute alcohol (94/6) to afford the title compound as a mixture of stereoisomers. 1H-NMR (CD3OD) rotamers: δ: 1.2-1.45 (m, 6H), 2.04 (m, 1H), 2.78 (m, 1H), 3.18 (m, 1H), 3.30-4.35 (m, 6H), 4.7-4.9 (m, 2H), 4.95, 5.0 (2d, 1H), 6.95-7.02 (m, 2H), 7.10-7.22 (m, 2H), 7.62 (s, 1H), 7.80 (s, 1H), 7.83 (s, 1H)ppm. MS: 516.2 (MH+) observed.

Provenance & Evidence