Dichloromethane → Trifluoroacetic acid

Participants

Reaction Steps

tert-Butyl (R)-1-(4-(2-ethoxythiazol-4-yl)phenyl)-4-((R)-3-(1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-4-oxobutan-2-ylcarbamate (97B) (0.091 mmol max, 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 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 (10-55% 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-(4-(2-ethoxythiazol-4-yl)phenyl)-1-((R)-3-(1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)butan-1-one (200) as its trifluoroacetic acid salt as a white flocculent solid (0.061 mmol, 0.041 g, 67% yield over 2-steps). ESI-MS: 562.2 m/z (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.39-1.66 (m, 1H) 1.67-2.12 (m, 5H) 2.28-2.44 (m, 2H) 2.56-2.95 (m, 4H) 2.94-3.28 (m, 7H) 3.84-4.05 (m, 1H) 4.09 (d, J=1.77 Hz, 5H) 4.44-4.61 (m, 1 H) 7.09-7.60 (m, 7H) 7.70-7.93 (m, 2H).

Provenance & Evidence