Hydrochloric Acid → HCID 18998842, compound

HRID 2260649Notes

Reaction equation

HRID 2260649 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[O:9])=[CH:4][CH:3]=1.[Cl:16][CH2:17][CH2:18][CH2:19][C:20]1([C:25]2[CH:30]=[CH:29][C:28]([NH:31][S:32]([CH3:35])(=[O:34])=[O:33])=[CH:27][CH:26]=2)OCC[O:21]1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+].Cl>C(O)CCC.O.C(OCC)(=O)C.CO>[ClH:16].[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH:10]2[CH2:15][CH2:14][N:13]([CH2:17][CH2:18][CH2:19][C:20]([C:25]3[CH:30]=[CH:29][C:28]([NH:31][S:32]([CH3:35])(=[O:34])=[O:33])=[CH:27][CH:26]=3)=[O:21])[CH2:12][CH2:11]2)=[O:9])=[CH:4][CH:3]=1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 27244404-(4-Fluorobenzoyl)piperidineHCID 18998867HCID 18998867, compound

Product 1

HCID 18998842HCID 18998842, compound

Reagents, catalysts & solvents 4

HCID 2631-ButanolSolventHCID 887MethanolSolvent2×HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 4-fluorophenyl-4-piperidinyl methanone (3.1 g, 15.0 mmol) and 2-(3-chloropropyl)-2-(4-methanesulfonamidophenyl)-1,3-dioxolane (4.70 g, 14.7 mmol) was prepared in n-butanol (50 mL), treated with potassium carbonate (2.00 g, 14.5 mmol) and a catalytic amount of potassium iodide, and refluxed for 18 hours. The cooled mixture was diluted with water and ethyl acetate. The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with water, brine, dried (MgSO4), filtered, and evaporated to an oil. The oil was dissolved in methanol (200 mL), treated with HCl (25 mL of a 10% solution in water), and stirred for 5 hours. The solution was concentrated, made basic with aqueous 5% sodium bicarbonate, and extracted twice with chloroform. The combined organic layers were washed with water, brine, dried (MgSO4), filtered, and evaporated to a yellow solid. The solid was chromatographed on silica gel, eluting with acetone. The appropriate fractions were combined and evaporated to afford a yellow solid. The solid was dissolved in methanol and treated with a slight excess of HCl in methanol. The solution was concentrated and the resulting solid was recrystallized from methanol/butanone to yield the desired product as a tan powder: mp 205°-210° C. (decomp.).

Workup

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted with ethyl acetate
  3. washThe combined organic layers were washed with water, brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated to an oil
  7. dissolutionThe oil was dissolved in methanol (200 mL)
  8. additiontreated with HCl (25 mL of a 10% solution in water), and
  9. concentrationThe solution was concentrated
  10. extractionextracted twice with chloroform
  11. washThe combined organic layers were washed with water, brine
  12. dry with materialdried (MgSO4)
  13. filtrationfiltered
  14. customevaporated to a yellow solid
  15. customThe solid was chromatographed on silica gel
  16. washeluting with acetone
  17. customevaporated
  18. customto afford a yellow solid
  19. concentrationThe solution was concentrated
  20. customthe resulting solid was recrystallized from methanol/butanone

Sources & evidence

ORD record
ord-b1d32ae2fd894f789ce426016f102079
Source dataset
uspto-grants-1995_12
Patent number
US05478846

Reaction notes

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