tert-Butyl acrylate → tert-butyl 3-[4-({[(3-isopropyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)carbonyl]amino}methyl)piperidin-1-yl]propanoate

HRID 736420Notes

Reaction equation

HRID 736420 reaction equation
[CH:1]([N:4]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[N:6]([C:13]([NH:15][CH2:16][CH:17]2[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]2)=[O:14])[C:5]1=[O:23])([CH3:3])[CH3:2].[C:24]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])(=[O:27])[CH:25]=[CH2:26]>C1COCC1.C([O-])(O)=O.[Na+]>[CH:1]([N:4]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[N:6]([C:13]([NH:15][CH2:16][CH:17]2[CH2:18][CH2:19][N:20]([CH2:26][CH2:25][C:24]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:21][CH2:22]2)=[O:14])[C:5]1=[O:23])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 15458tert-Butyl acrylateHCID 442491883-isopropyl-2-oxo-N-(piperidin-4-ylmethyl)-2,3-dihydro-1H-benzimidazole-1-carboxamide

Product 1

HCID 68585760tert-butyl 3-[4-({[(3-isopropyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)carbonyl]amino}methyl)piperidin-1-yl]propanoateYield 16%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A mixture of 3-isopropyl-2-oxo-N-(piperidin-4-ylmethyl)-2,3-dihydro-1H-benzimidazole-1-carboxamide (0.50 g, 1.58 mmol, Step2), tert-butyl acrylate (0.340 mL, 2.37 mmol) and iPrNEt (0.275 mL, 2.37 mmol) in THF (20 mL) was refluxed for 18 h. After cooling, the reaction mixture was diluted with sat. NaHCO3 aq. (100 mL), extracted with CH2Cl2 (100 mL) for three times. The combined extracts were dried over Na2SO4, filtered and concentrated. The residue was chromatographed on a column of silica gel eluted with MeOH/CH2Cl2 (1:20→1:10) and then NH-silica gel eluted with EtOAc/hexane (1:5→1:2) to give 0.111 g (16%) of title compound as colorless syrup.

Workup

  1. temperaturewas refluxed for 18 h
  2. temperatureAfter cooling
  3. extractionextracted with CH2Cl2 (100 mL) for three times
  4. dry with materialThe combined extracts were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was chromatographed on a column of silica gel
  8. washeluted with MeOH/CH2Cl2 (1:20→1:10)
  9. washNH-silica gel eluted with EtOAc/hexane (1:5→1:2)

Sources & evidence

ORD record
ord-25851591027f491a9e2c6d3973e2c63c
Source dataset
uspto-grants-2009_09
Patent number
US07595329B2

Reaction notes

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