4-Fluorobenzyl chloride → HCID 15624016, compound

HRID 1856559Notes

Reaction equation

HRID 1856559 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][CH:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][CH3:20])=[O:18])[CH2:13][CH:12]1[CH3:21].Cl[CH2:23][C:24]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O>[F:30][C:27]1[CH:28]=[CH:29][C:24]([CH2:23][N:1]2[C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[N:3]=[C:2]2[NH:10][CH:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][CH3:20])=[O:18])[CH2:13][CH:12]2[CH3:21])=[CH:25][CH:26]=1

Participants

5

Reactant 3

HCID 96024-Fluorobenzyl chlorideHCID 10340Sodium CarbonateHCID 15624015HCID 15624015, compound

Product 1

HCID 15624016HCID 15624016, compoundYield 38%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 19 parts of methyl 4-(1H-benzimidazol-2-ylamino)-3-methyl-1-piperidinecarboxylate, 11 parts of 1-(chloromethyl)-4-fluorobenzene, 6 parts of sodium carbonate and 135 parts of N,N-dimethylformamide is stirred and heated overnight at 70° C. The reaction mixture is cooled and poured onto water. The product is extracted three times with methylbenzene. The combined extracts are dried, filtered and evaporated. The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (96:4 by volume) as eluent. The pure fractions are collected and the eluent is evaporated. The residue is crystallized from a mixture of 2-propanone and 2,2'-oxybispropane. The product is filtered off and dried, yielding 8 parts (38%) of methyl 4-[1-(4-fluorophenylmethyl)-1H-benzimidazol-2-ylamino]-3-methyl-1-piperidinecarboxylate; mp. 172.5° C.

Workup

  1. temperatureThe reaction mixture is cooled
  2. additionpoured onto water
  3. extractionThe product is extracted three times with methylbenzene
  4. customThe combined extracts are dried
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue is purified by column-chromatography over silica gel using
  8. additiona mixture of trichloromethane and methanol (96:4 by volume) as eluent
  9. customThe pure fractions are collected
  10. customthe eluent is evaporated
  11. customThe residue is crystallized from a mixture of 2-propanone and 2,2'-oxybispropane
  12. filtrationThe product is filtered off
  13. customdried

Sources & evidence

ORD record
ord-a65879ec837f4160a8047a99766e98af
Source dataset
uspto-grants-1980_08
Patent number
US04219559

Reaction notes

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