Hydrochloric Acid → 4-(1-tert-Butoxycarbonyl-1,2,3,6-tetrahydropyridin-4-yl)benzoic acid

HRID 352754Notes

Reaction equation

HRID 352754 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11](OS(C(F)(F)F)(=O)=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:22]([C:25]1[CH:30]=[CH:29][C:28](OB(O)O)=[CH:27][CH:26]=1)([OH:24])=[O:23].[Cl-].[Li+].C(=O)([O-])[O-].[Na+].[Na+].Cl>COCCOC>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:28]2[CH:29]=[CH:30][C:25]([C:22]([OH:24])=[O:23])=[CH:26][CH:27]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 10991161Tert-butyl 4-(trifluoromethanesulfonyloxy)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 227099914-Carboxyphenylboric acid

Product 1

HCID 227102704-(1-tert-Butoxycarbonyl-1,2,3,6-tetrahydropyridin-4-yl)benzoic acid

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

In 1,2-dimethoxyethane (30 ml), 4-(1-tert-butoxycarbonyl-4-trifluoromethanesulfonyloxy-1,2,3,6-tetrahydropyridine (Synthesis, 993, 1991)(3.59 g) was dissolved, followed by the addition of 4-carboxyphenylboric acid (3.60 g), lithium chloride (1.38 g), tetrakistriphenylphosphine palladium (0.62 g) and an aqueous solution of sodium carbonate (2M, 16.3 ml). The resulting mixture was heated under reflux for 2 hours under an argon gas atmosphere. To the reaction mixture, 1N hydrochloric acid was added. The resulting mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate. The residue obtained by distilling off the solvent under reduced pressure was purified by chromatography on a silica gel column (dichloromethane˜dichloromethane:methanol=100:1). The purified product was pulverized and washed in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate=5:1), whereby the title compound (462 mg, 14%) was obtained.

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureunder reflux for 2 hours under an argon gas atmosphere
  3. extractionThe resulting mixture was extracted with ethyl acetate
  4. dry with materialThe extract was dried over anhydrous sodium sulfate
  5. customThe residue obtained
  6. distillationby distilling off the solvent under reduced pressure
  7. customwas purified by chromatography on a silica gel column (dichloromethane˜dichloromethane:methanol=100:1)
  8. washwashed in a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate=5:1), whereby the title compound (462 mg, 14%)
  9. customwas obtained

Sources & evidence

ORD record
ord-38996146318145c0ac55839d2dc07a65
Source dataset
uspto-grants-2004_06
Patent number
US06747023B1

Reaction notes

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