Sodium Carbonate → HCID 20385591, compound

HRID 46890Notes

Reaction equation

HRID 46890 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 30173591-(3-Chloropropyl)-1,3-dihydro-3-(1-methylvinyl)-2H-benzimidazol-2-one

Product 1

HCID 20385591HCID 20385591, compound

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-methylethenyl)-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 evaporated. 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. customthe eluent is evaporated
  9. dissolutionThe oily residue is dissolved in 2-propanone
  10. stirringthe whole is stirred
  11. temperaturerefluxed for 15 minutes
  12. customThe solvent is evaporated
  13. dissolutionthe formed hydrochloride salt is dissolved in water
  14. extractionThe product is extracted with 4-methyl-2-pentanone
  15. customThe extract is dried
  16. filtrationfiltered
  17. customevaporated
  18. customThe residue is crystallized from methylbenzene
  19. filtrationThe product is filtered off
  20. customdried

Sources & evidence

ORD record
ord-1e42806b433a42249c2a691680485946
Source dataset
uspto-grants-1979_11
Patent number
US04175129

Reaction notes

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