Potassium Iodide → [2-{4-[1-(4-fluorophenylmethyl)-1H-benzimidazol-2-ylamino]-1-piperidinyl}ethyl] 4-morpholinecarboxylate

HRID 1856573Notes

Reaction equation

HRID 1856573 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Cl.Cl.Cl[CH2:10][CH2:11][N:12]1[CH2:17][CH2:16][CH:15]([NH:18][C:19]2[N:23]([CH2:24][C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)[C:22]3[CH:32]=[CH:33][CH:34]=[CH:35][C:21]=3[N:20]=2)[CH2:14][CH2:13]1.[C:36](=O)([O-:38])[O-:37].[Na+].[Na+].[I-].[K+]>CN(C)C=O>[N:1]1([C:36]([O:38][CH2:10][CH2:11][N:12]2[CH2:17][CH2:16][CH:15]([NH:18][C:19]3[N:23]([CH2:24][C:25]4[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=4)[C:22]4[CH:32]=[CH:33][CH:34]=[CH:35][C:21]=4[N:20]=3)[CH2:14][CH2:13]2)=[O:37])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 8083MorpholineHCID 10340Sodium CarbonateHCID 12891728N-[1-(2-chloroethyl)-4-piperidinyl]-1-(4-fluorophenylmethyl)-1H-benzimidazol-2-amine dihydrochloride

Product 1

HCID 12891729[2-{4-[1-(4-fluorophenylmethyl)-1H-benzimidazol-2-ylamino]-1-piperidinyl}ethyl] 4-morpholinecarboxylateYield 12.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 0.9 parts of morpholine, 4.8 parts of N-[1-(2-chloroethyl)-4-piperidinyl]-1-(4-fluorophenylmethyl)-1H-benzimidazol-2-amine dihydrochloride, 3 parts of sodium carbonate, 0.1 parts of potassium iodide and 135 parts of N,N-dimethylformamide is stirred and heated overnight at 70° C. The reaction mixture is poured onto water and the product is extracted with methylbenzene. The extract is dried, filtered and evaporated. The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (98:2 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, yielding 0.6 parts (12.5%) of [2-{4-[1-(4-fluorophenylmethyl)-1H-benzimidazol-2-ylamino]-1-piperidinyl}ethyl] 4-morpholinecarboxylate; mp. 144.8° C.

Workup

  1. additionThe reaction mixture is poured onto water
  2. extractionthe product is extracted with methylbenzene
  3. customThe extract is dried
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue is purified by column-chromatography over silica gel using
  7. additiona mixture of trichloromethane and methanol (98:2 by volume) as eluent
  8. customThe pure fractions are collected
  9. customthe eluent is evaporated
  10. customThe residue is crystallized from a mixture of 2-propanone and 2,2'-oxybispropane

Sources & evidence

ORD record
ord-8311c6d8ef9c478b934f521030a81361
Source dataset
uspto-grants-1980_08
Patent number
US04219559

Reaction notes

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