Dichloromethane → Trifluoroacetic acid

Participants

Reaction Steps

tert-butyl (R)-1-(4′-(2-methoxyethylcarbamoyl)biphenyl-4-yl)-4-((R)-3-(1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-4-oxobutan-2-ylcarbamate (86B) (0.053 mmoles, 0.038 g) was added to a 10 mL round-bottomed flask equipped for stirring under nitrogen. Dichloromethane (1 mL) and trifluoroacetic acid (1 mL) were then added and the resultant solution was allowed to stir under nitrogen for 4 hrs. 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 (0.5-50% 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 4′-((R)-2-amino-4-((R)-3-(1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-4-oxobutyl)-N-(2-methoxyethyl)biphenyl-4-carboxamide (177) as its trifluoroacetic acid salt and as a white flocculent solid (0.033 mmoles, 0.024 g, 62% yield). ESI-MS: m/z 612.3 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.40-1.62 (m, 1H) 1.74-2.21 (m, 5H) 2.58-2.86 (m, 3H) 2.90-3.16 (m, 4H) 3.16-3.25 (m, 3H) 3.28 (s, 3H) 3.30-3.51 (m, 7H) 3.64-4.19 (m, 2H) 4.27-4.70 (m, 4H) 7.36-7.50 (m, 4H) 7.68-7.82 (m, 6H) 7.95 (dd, J=8.46, 2.40 Hz, 2H) 8.54-8.63 (m, 1H).

Provenance & Evidence