Trimethylsilyl iodide → Benzamide

Participants

Reaction Steps

To a solution of benzyl rac-(3R,4R)-3-(benzyloxy)-4-[({[3-(trifluoromethyl)benzoyl]amino}acetyl)amino]pyrrolidine-1-carboxylate in dichloromethane was slowly added TMSI (˜3 equiv.). After 1 hour, all volatiles were removed and the slurry was taken up in acetonitrile (3 mL). 1-(4-methoxyphenyl)piperidin-4-one and sodium triacetoxyborohydride were added and the reaction mixture was stirred overnight. To the mixture was added NaHCO3 (sat. aq., 10 mL) and dichloromethane (10 mL). The organic layer was separated and the aqueous layer was washed with an addition portion of dichloromethane (10 mL). The organic layers were combined, dried over Na2SO4, filtered and concentrated. The resulting crude product was subjected to flash chromatography (15% MeOH, 1% NH4OH in EtOAc) to afford N-[2-({(3R,4R)-4-benzyloxy)-1-[1-(4-methoxyphenyl)piperidin-4-yl]pyrrolidin-3-yl}amino)-2-oxoethyl]-3-trifluoromethyl)benzamide (55 mg overall) as a white solid. 1H-NMR (CDCl3) δ: 1.98-2.15 (m, 1H), 2.53-2.62 (m, 2H), 3.05-3.19 (m, 2H), 3.33-3.38 (m, 1H), 3.47-3.52 (d, J=12.3 Hz, 2H), 3.63-3.69 (m, 4M), 3.86-3.99 (m, 1H), 4.14-4.22 (m, 3H), 4.52-4.77 (m, 3H), 6.73-6.78 (m, 4H), 7.22-7.35 (m, 5H), 7.47-7.52 (t, J=7.6 Hz, 1H), 7.67-7.70 (d, J=7.5 Hz, 1H), 8.03-8.07 (m, 2H), 8.12 (s, 1H). MS m/z: 611 (M+1)

Provenance & Evidence