Dichloromethane → Trifluoroacetic acid

Participants

Reaction Steps

tert-Butyl (R)-1-(biphenyl-4-yl)-4-((R)-3-(4-chloro-1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-4-oxobutan-2-ylcarbamate (48C) (0.245 mmol, crude oil) was added to a 10 mL round-bottomed flask equipped for stirring under nitrogen. Dichloromethane (2 mL) and trifluoroacetic acid (2 mL) were then added and the solution was stirred at room temperature for 2 hr. The solvent was removed in-vacuo affording a clear colored oil. This oil was re-dissolved in methanol (3 mL), filtered, and then purified by preparative LC/MS (15-65% CH3CN in H2O). The resultant fractions were collected and the solvent was removed in-vacuo affording a clear colored oil. This oil was re-dissolved in CH3CN (1 mL) and water (2 mL). The resultant solution was frozen and lyophilized to afford (R)-3-amino-4-(biphenyl-4-yl)-1((R)-3-(4-chloro-1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)butan-1-one (118) as its trifluoroacetic acid salt and as a white flocculent solid (0.134 mmol, 0.088 g, 55% yield over 4-steps). ESI-MS: 545.2 m/z (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.40-1.55 (m, 1H) 1.70-2.14 (m, 5H) 2.61-2.87 (m, 3H) 2.87-3.09 (m, 4H) 3.09-3.31 (m, 5H) 3.40-3.85 (m, 2H) 3.95-4.62 (m, 5H) 7.17-7.30 (m, 2H) 7.33-7.42 (m, 3H) 7.42-7.56 (m, 3H) 7.58-7.72 (m, 4H).

Provenance & Evidence