Trifluoroacetic acid → HCID 66796747, compound

Participants

Reaction Conditions

Reaction Steps

To a mixture of ethyl 1-(4-bromo-2-fluorophenyl)-2-(2-(2,6-dichlorophenyl)propan-2-yl)-4-hydroxy-4,5-dihydro-1H-imidazole-4-carboxylate (38 g, 73 mmol) in EtOH (200 mL) was added TFA (25.0 g, 220 mmol). The mixture was subsequently heated to 95° C. HPLC analysis after 2.5 hours showed <1% of alcohol intermediate remaining The mixture was diluted with 300 mL of CH2Cl2 and cooled to approximately 5° C. with an ice bath. The mixture was neutralized with 1N NaOH (120 mL) and the organic layer was separated. The aqueous layer was extracted with CH2Cl2 (2×100 mL). The combined organic layers were concentrated on a rotary evaporator to give crude material. Recrystallization in EtOH (5 mL/1 g) provided 32 g of ethyl 1-(4-bromo-2-fluorophenyl)-2-(2-(2,6-dichlorophenyl)propan-2-yl)-1H-imidazole-4-carboxylate as an off-white solid (86% yield). 1H-NMR (DMSO-d6, 400 MHz) δ 7.92 (s, 1H), 7.16 (d, 1H, J=8.0 Hz), 7.22 (m, 3H), 7.11 (m, 1H), 7.04 (t, 1H, J=12.0 Hz), 4.25 (q, 2H, J=8.0 Hz), 1.94 (s, 6H), 1.27 (t, 3H, J=8.0 Hz); MS m/e 502.68 (M+H+); HPLC (XBridge 5μ C18 4.6×50 mm, 4 mL/min, Solvent A: 10% MeOH/water with 0.2% H3PO4, Solvent B: 90% MeOH/water with 0.2% H3PO4, gradient with 0-100% B over 4 minutes): 3.87 minutes.

Provenance & Evidence