Sodium Bicarbonate → HCID 22495591, compound

HRID 1815837Notes

Reaction equation

HRID 1815837 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11](O)([C:14]2[C:22]3[O:21][CH:20]=[CH:19][C:18]=3[CH:17]=[C:16]([F:23])[CH:15]=2)[CH:10]([CH3:25])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.C(OCC)(=O)C.[OH-].[NH4+]>[CH2:1]([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[C:22]3[O:21][CH:20]=[CH:19][C:18]=3[CH:17]=[C:16]([F:23])[CH:15]=2)[CH:10]([CH3:25])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([C:14]2[C:22]3[O:21][CH:20]=[CH:19][C:18]=3[CH:17]=[C:16]([F:23])[CH:15]=2)=[C:10]([CH3:25])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 3

HCID 516892Sodium BicarbonateHCID 521998p-Toluenesulfonic acid monohydrateHCID 22495650HCID 22495650, compound

Product 2

HCID 22495538HCID 22495538, compoundYield 8%HCID 22495591HCID 22495591, compoundYield 79%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolventHCID 14923Ammonium HydroxideSolvent

Procedure

A mixture of 5.78 gm (17 mMol) 1-benzyl-3-methyl-4-hydroxy-4-(5-fluorobenzofur-7-yl)piperidine and 10 gm (52.6 mMol) p-toluenesulfonic acid monohydrate in 100 mL toluene was heated at reflux for 24 hours. The reaction mixture was cooled to room temperature and was diluted with 200 mL ethyl acetate followed by 100 mL saturated aqueous sodium bicarbonate and 100 mL IN ammonium hydroxide. The phases were separated and the aqueous phase extracted with 2×100 mL ethyl acetate. The combined organic phases were washed with 100 mL saturated aqueous sodium chloride, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel chromatography, eluting with a gradient of hexane containing from 0-50% ethyl acetate. Recovered starting material (4.38 gm) was subjected again to the dehydration conditions in 200 mL toluene. Fractions containing product from both dehydration runs were combined and concentrated under reduced pressure to provide 4.3 gm (79%) 1-benzyl-3-methyl-4-(5-fluorobenzofur-7-yl)-1,2,3,6-tetrahydropyridine and 0.45 gm (8%) 1-benzyl-3-methyl-4-(5-fluorobenzofur-7-yl)-1,2,5,6-tetrahydropyridine.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 24 hours
  3. customThe phases were separated
  4. extractionthe aqueous phase extracted with 2×100 mL ethyl acetate
  5. washThe combined organic phases were washed with 100 mL saturated aqueous sodium chloride
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. washeluting with a gradient of hexane containing from 0-50% ethyl acetate
  9. customRecovered
  10. additionFractions containing product from both dehydration runs
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-ecbd55b52b5144e5a5485feeee968344
Source dataset
uspto-grants-2005_04
Patent number
US06881733B1

Reaction notes

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