Sodium Carbonate → 1-{3-[4-(4-fluorophenyl)-4-hydroxy-1-piperidinyl]propyl}-1,3-dihydro-2H-benzimidazol-2-one

HRID 1833659Notes

Reaction equation

HRID 1833659 reaction equation
Cl[CH2:2][CH2:3][CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[N:7](C(C)C)[C:6]1=[O:17].[F:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2([OH:31])[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]2)=[CH:21][CH:20]=1.C(=O)([O-])[O-].[Na+].[Na+].[OH-].[Na+]>O.CC(C)CC(=O)C>[F:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2([OH:31])[CH2:26][CH2:27][N:28]([CH2:2][CH2:3][CH2:4][N:5]3[C:9]4[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=4[NH:7][C:6]3=[O:17])[CH2:29][CH2:30]2)=[CH:21][CH:20]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 774974-(4-Fluorophenyl)piperidin-4-olHCID 20291980HCID 20291980, compound

Product 1

HCID 203855911-{3-[4-(4-fluorophenyl)-4-hydroxy-1-piperidinyl]propyl}-1,3-dihydro-2H-benzimidazol-2-one

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 7909Methyl Isobutyl KetoneSolvent

Procedure

A mixture of 5 parts of 1-(3-chloropropyl)-1,3-dihydro-3-(1-methylethyl)-2H-benzimidazol-2-one, 3.9 parts of 4-(4-fluorophenyl)-4-piperidinol, 5.3 parts of sodium carbonate and 80 parts of 4-methyl-2-pentanone is stirred and refluxed for 48 hours with water-separator. The reaction mixture is cooled to room temperature, water is added and the whole is alkalized with 15 parts of a sodium hydroxide solution 60%. The layers are separated and the organic phase is dried, filtered and evaporated. The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and 10% of methanol as eluent. The pure fractions are collected and the eluent is evaported. The oily residue is dissolved in 2-propanone. The solution is acidified with 2-propanol, previously saturated with gaseous hydrogen chloride, and the whole is stirred and refluxed for 15 minutes. The solvent is evaporated and the formed hydrochloride salt is dissolved in water. The free base is liberated in the conventional manner with a diluted sodium hydroxide solution. The product is extracted with 4-methyl-2-pentanone. The extract is dried, filtered and evaporated. The residue is crystallized from methylbenzene. The product is filtered off and dried, yielding 2.5 parts of 1-{3-[4-(4-fluorophenyl)-4-hydroxy-1-piperidinyl]propyl}-1,3-dihydro-2H-benzimidazol-2-one; mp. 135.4° C.

Workup

  1. customThe layers are separated
  2. customthe organic phase is dried
  3. filtrationfiltered
  4. customevaporated
  5. customThe residue is purified by column-chromatography over silica gel using
  6. additiona mixture of trichloromethane and 10% of methanol as eluent
  7. customThe pure fractions are collected
  8. dissolutionThe oily residue is dissolved in 2-propanone
  9. stirringthe whole is stirred
  10. temperaturerefluxed for 15 minutes
  11. customThe solvent is evaporated
  12. dissolutionthe formed hydrochloride salt is dissolved in water
  13. extractionThe product is extracted with 4-methyl-2-pentanone
  14. customThe extract is dried
  15. filtrationfiltered
  16. customevaporated
  17. customThe residue is crystallized from methylbenzene
  18. filtrationThe product is filtered off
  19. customdried

Sources & evidence

ORD record
ord-9a270256faa34378ac81a9c8a002b80f
Source dataset
uspto-grants-1978_01
Patent number
US04066772

Reaction notes

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