Carbonocyanidic acid, methyl ester → Methyl 1-[1-(1-Phenylcycloheptyl)-4-piperidinyl]-1H-benzimidazole-2-carboxylate

HRID 982632Notes

Reaction equation

HRID 982632 reaction equation
[C:1]1([C:7]2([N:14]3[CH2:19][CH2:18][CH:17]([N:20]4[C:24]5[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=5[N:22]=[CH:21]4)[CH2:16][CH2:15]3)[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Li]CCCC.C([C:36]([O:38][CH3:39])=[O:37])#N>C1COCC1.CN(P(N(C)C)(N(C)C)=O)C>[C:1]1([C:7]2([N:14]3[CH2:15][CH2:16][CH:17]([N:20]4[C:24]5[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=5[N:22]=[C:21]4[C:36]([O:38][CH3:39])=[O:37])[CH2:18][CH2:19]3)[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 3

HCID 28660Carbonocyanidic acid, methyl esterHCID 225621971-[1-(1-phenylcycloheptyl)-4-piperidinyl]-1H-benzimidazoleHCID 178418339Butyllithium

Product 1

HCID 10181181Methyl 1-[1-(1-Phenylcycloheptyl)-4-piperidinyl]-1H-benzimidazole-2-carboxylateYield 17%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 12679HexamethylphosphoramideSolvent

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of 1-[1-(1-phenylcycloheptyl)-4-piperidinyl]-1H-benzimidazole (as prepared in WO 00/008013, 7.828 g, 20.957 mmol) in THF (200 ml) and HMPA (70 ml) was added dropwise a solution of n-BuLi (1.54 M solution in hexane, 20.4 ml, 31.435 mmol) at −78° C. After 1 hour stirring at −78° C., methyl cyanoformate was added to the reaction mixture at −78° C. After 2 hours stirring, the reaction mixture was quenched with NH4Cl solution and warmed to room temperature. The reaction mixture was extracted with ethyl acetate. The extracts combined were washed with NaHCO3 solution and brine, dried (Na2SO4), filtered, and concentrated to give oil. This oil was purified by column chromatography (silica gel:200 g, ethyl acetate/n-hexane:1/2 as an eluent) to afford 1.53 g (17%) of title compound as colorless foam.

Workup

  1. stirringAfter 2 hours stirring
  2. customthe reaction mixture was quenched with NH4Cl solution
  3. temperaturewarmed to room temperature
  4. extractionThe reaction mixture was extracted with ethyl acetate
  5. washThe extracts combined were washed with NaHCO3 solution and brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give oil
  10. customThis oil was purified by column chromatography (silica gel

Sources & evidence

ORD record
ord-2cdf8fef6c0d49c19413180dc97a8afe
Source dataset
uspto-grants-2005_03
Patent number
US06861425B2

Reaction notes

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