tert-Butanol → HCID 9798365, compound

HRID 1016443Notes

Reaction equation

HRID 1016443 reaction equation
[CH2:1]([CH:8]1[CH2:13][CH2:12][N:11]([CH:14]([CH3:30])[CH2:15][CH2:16][C:17]2[N:21](CCC#N)[C:20]3[CH:26]=[CH:27][CH:28]=[CH:29][C:19]=3[N:18]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(C)(C)C.CC(C)([O-])C.[K+].C(OCC)(=O)C>C(=O)(O)[O-].[Na+].C(N(CC)CC)C.CO>[CH2:1]([CH:8]1[CH2:9][CH2:10][N:11]([CH:14]([CH3:30])[CH2:15][CH2:16][C:17]2[NH:18][C:19]3[CH:29]=[CH:28][CH:27]=[CH:26][C:20]=3[N:21]=2)[CH2:12][CH2:13]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 6386tert-ButanolHCID 8857Ethyl AcetateHCID 18407013HCID 18407013, compoundHCID 23665647Potassium tert-butoxide

Product 1

HCID 9798365HCID 9798365, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8471TriethylamineSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A mixture of 0.32 g of 3-{2-[3-(4-benzyl-piperidin-1-yl)-butyl]-benzimidazol-1-yl}-propionitrile, 100 mL of tert-butanol and 1 g of potassium tert-butoxide was heated to reflux for 10 min. Conversion was complete by TLC (80:20:1 ethyl acetate:methanol:triethylamine). The mixture was cooled, diluted with 10 mL of saturated sodium bicarbonate and concentrated. The residue was partitioned between 3×100 mL of chloroform and 50 mL of water. After drying over magnesium sulfate and concentration under reduced pressure, the residue was purified by preparative TLC eluting with 90:10:2 chloroform:methanol:ammonium hydroxide. The major band (UV visualization) was 2-[3-(4-benzyl-piperidin-1-yl)-butyl]-1H-benzimidazole (250 mg): MS (m+1)=348.5; 1H NMR (400 MHz, CDCl3) 7.42 (s, 2H), 7.3 (m, 2H), 7.25 (m, 1H), 7.2 (m, 4H), 3.25 (m, 1H), 3.0 (m, 2H), 2.8 (d, 2H), 2.65 (m, 2H), 2.5 (m, 2H), 2.1 (m, 2H), 1.6 (d, 2H), 1.3 (m, 1H), 1.2 (d, 3H), 1.0 (m, 1H).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 10 min
  3. temperatureThe mixture was cooled
  4. concentrationconcentrated
  5. customThe residue was partitioned between 3×100 mL of chloroform and 50 mL of water
  6. dry with materialAfter drying over magnesium sulfate and concentration under reduced pressure
  7. customthe residue was purified by preparative TLC
  8. washeluting with 90:10:2 chloroform

Sources & evidence

ORD record
ord-2c056ff089cc4ba483aad7a8b975b9b1
Source dataset
uspto-grants-2002_11
Patent number
US06476041B1

Reaction notes

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