Hydrochloric Acid → (Z)-2,3-Dihydro-2-[1-[3-(2-phenoxyphenyl)-2-propenyl]-4-piperidinyl]-1H-isoindol-1-one, monohydrochloride

HRID 1108522Notes

Reaction equation

HRID 1108522 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([N:7]2[CH2:15][C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[C:8]2=[O:16])[CH2:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].[CH2:23]([O:25][CH2:26][CH3:27])[CH3:24].[ClH:28]>CN(C=O)C.CO>[ClH:28].[O:25]([C:26]1[CH:2]=[CH:3][CH:4]=[CH:5][C:27]=1/[CH:12]=[CH:13]\[CH2:14][N:1]1[CH2:6][CH2:5][CH:4]([N:7]2[CH2:15][C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[C:8]2=[O:16])[CH2:3][CH2:2]1)[C:23]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:24]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 3283Diethyl Ether2×HCID 11430Potassium CarbonateHCID 154319612-(Piperidin-4-yl)isoindolin-1-one

Product 1

HCID 131721195(Z)-2,3-Dihydro-2-[1-[3-(2-phenoxyphenyl)-2-propenyl]-4-piperidinyl]-1H-isoindol-1-one, monohydrochlorideYield 80%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
55 °C

Procedure

To a solution of Part E compound (600 mg, 2.45 mmol) in DMF (20 mL) was added Example 2 Part A compound (2-(4-piperidinyl)-2,3-dihydro-1H-isoindol-1-one) (530 mg, 2.45 mmol) followed by anhydrous potassium carbonate (372 mg, 2.69 mmol). The reaction was stirred at 55° C. overnight. The reaction was cooled to RT. Ethyl ether (200 mL) was added to dilute the reaction, and the organic layer was washed with water (2×50 mL), brine (2×50 mL) and dried over MgSO4. Evaporation gave a crude oil. Purification was performed by flash chromatography on 100 g of silica gel, loaded and eluted with 2% methanol in dichloromethane. Pure fractions were combined and evaporated to give a colorless oil. The resulting oil was dissolved in methanol (2 mL) and HCl in ethyl ether solution (1.0 M, 3.0 mL, 3.0 mmol) was added. The HCl salt precipitated from the solution. The salt was filtered and dried at 60° C. under vacuum to give title compound (490 mg, 80%) as a white solid.

Workup

  1. temperatureThe reaction was cooled to RT
  2. additionto dilute
  3. customthe reaction
  4. washthe organic layer was washed with water (2×50 mL), brine (2×50 mL)
  5. dry with materialdried over MgSO4
  6. customEvaporation
  7. customgave a crude oil
  8. customPurification
  9. washeluted with 2% methanol in dichloromethane
  10. customevaporated
  11. customto give a colorless oil
  12. customThe HCl salt precipitated from the solution
  13. filtrationThe salt was filtered
  14. customdried at 60° C. under vacuum

Sources & evidence

ORD record
ord-f610984f972147969b92acd569a4c3fb
Source dataset
uspto-grants-2000_05
Patent number
US06066650

Reaction notes

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