Dimethylformamide → 4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]methyl]-N,N-dimethyl-alpha,alpha-diphenyl-1-piperidinebutanamide

HRID 1904839Notes

Reaction equation

HRID 1904839 reaction equation
[Br-].[C:2]1([C:8]2([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH2:12][CH2:11][O:10][C:9]2=[N+:13]([CH3:15])[CH3:14])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:22][C:23]1[CH:28]=[CH:27][C:26]([CH2:29][N:30]2[C:34]3[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=3[N:32]=[C:31]2[CH2:39][CH:40]2[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]2)=[CH:25][CH:24]=1.C(=O)([O-])[O-].[Na+].[Na+].CN(C)C=O>O>[F:22][C:23]1[CH:28]=[CH:27][C:26]([CH2:29][N:30]2[C:34]3[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=3[N:32]=[C:31]2[CH2:39][CH:40]2[CH2:41][CH2:42][N:43]([CH2:11][CH2:12][C:8]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)([C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[C:9]([N:13]([CH3:15])[CH3:14])=[O:10])[CH2:44][CH2:45]2)=[CH:25][CH:24]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 2723589(Dihydro-3,3-diphenyl-3H-furan-2-ylidene)dimethylammonium bromideHCID 140128661-[(4-fluorophenyl)methyl]-2-(4-piperidinylmethyl)-1H-benzimidazole

Product 1

HCID 145180254-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]methyl]-N,N-dimethyl-alpha,alpha-diphenyl-1-piperidinebutanamideYield 20%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 5.55 parts of N-(dihydro-3,3-diphenyl-2(3H)-furanylidene)-N-methylmethanaminium bromide, 4.85 parts of 1-[(4-fluorophenyl)methyl]-2-(4-piperidinylmethyl)-1H-benzimidazole, 2 parts of sodium carbonate and 90 parts of N,N-dimethylformamide was stirred overnight at 70° C. The reaction mixture was poured into water. The product was extracted with 4-methyl-2-pentanone. The extract was dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol, saturated with ammonia, (95:5 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from acetonitrile. The product was filtered off and dried, yielding 1.8 parts (20%) of 4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]methyl]-N,N-dimethyl-α,α-diphenyl-1-piperidinebutanamide; mp. 151.4° C. (150).

Workup

  1. extractionThe product was extracted with 4-methyl-2-pentanone
  2. customThe extract was dried
  3. filtrationfiltered
  4. customevaporated
  5. customThe residue was purified by column chromatography over silica gel using
  6. additiona mixture of trichloromethane and methanol
  7. customThe pure fractions were collected
  8. customthe eluent was evaporated
  9. customThe residue was crystallized from acetonitrile
  10. filtrationThe product was filtered off
  11. customdried

Sources & evidence

ORD record
ord-aaee2288e2ea4c6cace916e8765226fe
Source dataset
uspto-grants-1989_06
Patent number
US04839374

Reaction notes

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