Dichloromethane → Ethyl 4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-YL]amino]piperidine-1-carboxylate

HRID 323192

Reaction equation

HRID 323192 reaction equation
[F:1][C:2]1[CH:18]=[CH:17][C:5]([CH2:6][N:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[N:9]=[C:8]2Cl)=[CH:4][CH:3]=1.[NH2:19][CH:20]1[CH2:25][CH2:24][N:23]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:22][CH2:21]1.ClCCl>C(OCC)(=O)C.ClCCl>[F:1][C:2]1[CH:18]=[CH:17][C:5]([CH2:6][N:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[N:9]=[C:8]2[NH:19][CH:20]2[CH2:21][CH2:22][N:23]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:24][CH2:25]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 100867Ethyl 4-amino-1-piperidinecarboxylateHCID 30202411-(4-Fluorobenzyl)-2-chlorobenzimidazole

Product 1

HCID 3019916Ethyl 4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-YL]amino]piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 21226138Dichloromethane ethylacetateSolvent

Procedure

Combine 1-(4-fluorobenzyl)-2-chloro-1H-benzimidazole (22.1 g, 84 mmol) and ethyl 4-aminopiperidine-1-carboxylate (27.7 g, 161 mmol) and heat to 170° C. After 4 hours, partition the reaction mixture between aqueous 2.5 M sodium hydroxide solution and chloroform. Separate the layers and extract the aqueous layer twice with chloroform. Combine the organic layers, dry over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on a short column of silica gel eluting sequentially with dichloromethane and then 15% ethyl acetate/dichloromethane. Evaporate the product containing fractions, triturate with hexane, filter, and dry to give (1-(4-fluorobenzyl)-1H-benzimidazol-2-yl)-(1-ethoxycarbonyl-piperidin-4-yl)amine as a solid.

Workup

  1. custompartition the reaction mixture between aqueous 2.5 M sodium hydroxide solution and chloroform
  2. customSeparate the layers
  3. extractionextract the aqueous layer twice with chloroform
  4. dry with materialdry over Na2SO4
  5. filtrationfilter
  6. customevaporate in vacuo
  7. customto give a residue
  8. customEvaporate the product
  9. additioncontaining fractions
  10. customtriturate with hexane
  11. filtrationfilter
  12. customdry

Sources & evidence

ORD record
ord-02984ae1073d4d01893c349c925bac66
Source dataset
uspto-grants-2001_04
Patent number
US06211199B1

Linked notes

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