反应详情

(R)-tert-Butyl 3-(3-chloro-2-(3-methoxypropylamino)phenylcarbamoyl)piperidine-1-carboxylate (30C) (crude material, 2.23 mmol max) was added to a 50 mL round-bottomed flask equipped for stirring under nitrogen. Glacial acetic acid (10 mL) was then added and the resultant solution was stirred at 70° C. under nitrogen for 16 hr. Analysis of the reaction mixture at this time by LC/MS indicated that the reaction was complete. The reaction solution was then concentrated in-vacuo to give a brownish oil. Toluene (30 mL) was added and the subsequent solution was concentrated in vacuo. This dissolution in toluene and re-concentration was repeated three times to remove any trace quantities of acetic acid affording (R)-tert-butyl 3-(7-chloro-1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidine-1-carboxylate (30D) as a brown oil. This oil was then purified by preparative LC/MS (25-85% CH3CN in H2O) to afford the title compound 30D as a tan oil (0.233 mmol, 0.095 g, 10% yield over 3-steps). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.39 (s, 9H) 1.46-1.60 (m, 1H) 1.72-1.96 (m, 2H) 1.97-2.12 (m, 3H) 2.77-2.92 (m, 1H) 3.02-3.15 (m, 2H) 3.24 (s, 3H) 3.29-3.40 (m, 2H) 3.93-4.02 (m, 1H) 4.12 (br. s., 1H) 4.51-4.59 (m, 2H) 7.20 (t, J=7.83 Hz, 1H) 7.28 (d, J=7.83 Hz, 1H) 7.58 (d, J=7.83 Hz, 1H) ESI-MS: m/z 408.2 (M+H)+.

1. customequipped
2. concentrationThe reaction solution was then concentrated in-vacuo
3. customto give a brownish oil
4. concentrationthe subsequent solution was concentrated in vacuo
5. dissolutionThis dissolution in toluene
6. concentrationre-concentration
7. customto remove any trace quantities of acetic acid