Acetic Acid → (R)-tert-Butyl 3-(1H-benzo[d]imidazol-2-yl)piperidine-1-carboxylate

HRID 1096596Notes

Reaction equation

HRID 1096596 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9]([C@@H:11]1[CH2:16][CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12]1)=O.C(O)(=O)C>C1(C)C=CC=CC=1>[NH:8]1[C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[N:1]=[C:9]1[C@@H:11]1[CH2:16][CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12]1

Participants

4

Reactant 2

HCID 176Acetic AcidHCID 59918936(R)-tert-Butyl 3-(2-aminophenylcarbamoyl)piperidine-1-carboxylate

Product 1

HCID 66791508(R)-tert-Butyl 3-(1H-benzo[d]imidazol-2-yl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

(R)-tert-Butyl 3-(2-aminophenylcarbamoyl)piperidine-1-carboxylate (7A) (2.80 g, 8.77 mmol) was added to a 100 mL round-bottomed flask equipped for stirring under nitrogen. Glacial acetic acid (20 mL) was then added and the resultant solution was stirred at 65° C. under nitrogen for 2 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 was repeated three times to remove any trace quantities of acetic acid affording (R)-tert-Butyl 3-(1H-benzo[d]imidazol-2-yl)piperidine-1-carboxylate (7B) as a tannish-white solid. (13.94 mmol, 4.2 g, 80% over 2-steps). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.34-1.52 (m, 10H) 1.73-1.83 (m, 2H) 2.10-2.17 (br. s. 1H) 2.79-2.96 (m, 2H) 3.89-3.96 (br. s., 1H) 4.08-4.33 (br.s., 1H) 4.33-4.43 (br.s, 1H) 7.09-7.18 (dd, 2H, 8.97 Hz, 6.19 Hz) 7.39-7.48 (d, 1H, 6.82 Hz) 7.49-7.57 (d, 1H, 7.07 Hz) 12.27 (s, 1H) ESI-MS: adz 302.4 (M+H)+.

Workup

  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. customto remove any trace quantities of acetic acid

Sources & evidence

ORD record
ord-2014d5cc17af45abbb35c42acda78060
Source dataset
uspto-grants-2012_03
Patent number
US08138168B1

Reaction notes

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