p-Toluenesulfonic acid → ethyl 4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]amino]hexahydro-1H-azepine-1-carboxylate

HRID 1886402Notes

Reaction equation

HRID 1886402 reaction equation
O=[C:2]1[CH2:8][CH2:7][CH2:6][N:5]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:4][CH2:3]1.[F:14][C:15]1[CH:20]=[CH:19][C:18]([CH2:21][N:22]2[C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=3[N:24]=[C:23]2[NH2:31])=[CH:17][CH:16]=1.CC1C=CC(S(O)(=O)=O)=CC=1.[BH4-].[Na+]>CO.O.C(O)C.CC1C=CC=CC=1>[F:14][C:15]1[CH:16]=[CH:17][C:18]([CH2:21][N:22]2[C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=3[N:24]=[C:23]2[NH:31][CH:2]2[CH2:8][CH2:7][CH2:6][N:5]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:4][CH2:3]2)=[CH:19][CH:20]=1

Participants

9

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 30193052-amino-1-((4-fluorophenyl)methyl)-1H-benzimidazoleHCID 4311764Sodium borohydrideHCID 126660861-Carbethoxyazepan-4-one

Product 1

HCID 15037357ethyl 4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]amino]hexahydro-1H-azepine-1-carboxylateYield 100%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 887MethanolSolventHCID 962WaterSolvent2×HCID 1140TolueneSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 33.3 parts of ethyl hexahydro-4-oxo-1H-azepine-1-carboxylate, 36.15 parts of 1-(4-fluorophenylmethyl)-1H-benzimidazol-2-amine, 320 parts of methylbenzene and 0.1 parts of 4-methylbenzene-sulfonic acid was stirred overnight at reflux temperature using a water separator. After cooling to 50° C., 80 parts of ethanol were added. 4.2 Parts of sodium tetrahydroborate were added portionwise and upon completion, stirring was continued for 2 hours at 50° C. After cooling, water and 4.8 parts of methanol were added while stirring. The layers were separated and the aqueous layer was extracted with methylbenzene. The combined organic layers were dried, filtered and evaporated, yielding 73 parts (100%) of ethyl 4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]amino]hexahydro-1H-azepine-1-carboxylate as a residue (compound 20).

Workup

  1. temperatureat reflux temperature
  2. stirringstirring
  3. waitwas continued for 2 hours at 50° C
  4. temperatureAfter cooling
  5. stirringwhile stirring
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted with methylbenzene
  8. customThe combined organic layers were dried
  9. filtrationfiltered
  10. customevaporated

Sources & evidence

ORD record
ord-95df3a2ef0f54ec8aab0f221c80597a4
Source dataset
uspto-grants-1992_09
Patent number
US05151424

Reaction notes

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