Sodium hydride → 1-[(2-methyl-5-oxazolyl)methyl]-2-[[1-(phenylmethyl)-4-piperidinyl]methyl]-1H-benzimidazole

HRID 1197823Notes

Reaction equation

HRID 1197823 reaction equation
[C:1]1([CH2:7][N:8]2[CH2:13][CH2:12][CH:11]([CH2:14][C:15]3[NH:19][C:18]4[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=4[N:16]=3)[CH2:10][CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].Br[CH2:27][C:28]1[O:32][C:31]([CH3:33])=[N:30][CH:29]=1>CN(C)C=O>[CH3:33][C:31]1[O:32][C:28]([CH2:27][N:19]2[C:18]3[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=3[N:16]=[C:15]2[CH2:14][CH:11]2[CH2:10][CH2:9][N:8]([CH2:7][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH2:13][CH2:12]2)=[CH:29][N:30]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 128087865-(Bromomethyl)-2-methyloxazoleHCID 140128452-[[1-(phenylmethyl)-4-piperidinyl]methyl]-1H-benzimidazole

Product 1

HCID 191050241-[(2-methyl-5-oxazolyl)methyl]-2-[[1-(phenylmethyl)-4-piperidinyl]methyl]-1H-benzimidazoleYield 42%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 26 parts of 2-[[1-(phenylmethyl)-4-piperidinyl]methyl]-1H-benzimidazole in 282 parts of N,N-dimethylformamide there were added 4.8 parts of a dispersion of sodium hydride in mineral oil (50%) under a nitrogen atmosphere. After stirring for 1 hour, there was added portionwise a solution of 15 parts of 5-(bromomethyl)-2-methyloxazole in 47 parts of N,N-dimethylformamide, while cooling in an ice-bath (<20° C.). The whole was stirred for 18 hours and allowed to warm to room temperature. The oily layer was separated and discarded. The N,N-dimethylformamide layer was poured into water and the whole was extracted with 4-methyl-2-pentanone (3×). The combined extracts were washed with water, dried, filtered and evaporated. The residue was purified by column chromatography (silica gel; CH2Cl2 /CH3OH 90:10). The eluent of the desired fraction was evaporated and the residue was successively crystallized from 2,2'-oxybispropane and acetonitrile, yielding 14.31 parts (42.0%) of 1-[(2-methyl-5-oxazolyl)methyl]-2-[[1-(phenylmethyl)-4-piperidinyl]methyl]-1H-benzimidazole; mp. 108.6° C. (comp. 1).

Workup

  1. temperaturewhile cooling in an ice-bath (<20° C.)
  2. stirringThe whole was stirred for 18 hours
  3. customThe oily layer was separated
  4. additionThe N,N-dimethylformamide layer was poured into water
  5. extractionthe whole was extracted with 4-methyl-2-pentanone (3×)
  6. washThe combined extracts were washed with water
  7. customdried
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue was purified by column chromatography (silica gel; CH2Cl2 /CH3OH 90:10)
  11. customThe eluent of the desired fraction was evaporated
  12. customthe residue was successively crystallized from 2,2'-oxybispropane and acetonitrile

Sources & evidence

ORD record
ord-961fa878163f4e808996dccda02f8ee0
Source dataset
uspto-grants-1994_01
Patent number
US05278165

Reaction notes

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