Sodium hydride → HCID 23146863, compound

HRID 1260913Notes

Reaction equation

HRID 1260913 reaction equation
[H-].[Na+].Cl.[CH2:4]([N:11]1[CH2:16][CH2:15][CH:14]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:13](=O)[CH2:12]1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[CH:23]1[CH:28]=[CH:27][C:26](N(S(C(F)(F)F)(=O)=O)S(C(F)(F)F)(=O)=O)=[CH:25][CH:24]=1>CN(C=O)C>[CH2:4]([N:11]1[CH2:12][C:13]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[C:14]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:15][CH2:16]1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 142176Phenyl triflimideHCID 2723880Ethyl 1-benzyl-3-oxopiperidine-4-carboxylate hydrochloride

Product 1

HCID 23146863HCID 23146863, compoundYield 49.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of sodium hydride (60% in oil, 6.36 g) in DMF (100 mL) was added ethyl 1-benzyl-3-oxopiperidine-4-carboxylate monohydrochloride (19.0 g) at 0° C., and the mixture was stirred for 5 min. N-phenylbis(trifluoromethanesulfonimide) (25.0 g) was added, and the mixture was stirred at 0° C. for 1 hr. The reaction mixture was poured into ice water, and the resultant product was extracted with ethyl acetate. The organic layer was washed with water and brine and dried, and the solvent was evaporated under reduced pressure. To a mixture of the obtained residue in toluene (125 mL) and water (7.5 mL) were added dihydroxyphenylborane (5.82 g), potassium carbonate (4.40 g) and tetrakis(triphenylphosphine)palladium(0) (3.67 g), and the mixture was stirred under an argon atmosphere at 100° C. for 14 hr. The reaction mixture was poured into water, and the resultant product was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and brine and dried, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (solvent gradient; 10→20% ethyl acetate/hexane) to give ethyl 1-benzyl-5-phenyl-1,2,3,6-tetrahydropyridine-4-carboxylate (10.2 g) as a pale yellow oil.

Workup

  1. stirringthe mixture was stirred at 0° C. for 1 hr
  2. extractionthe resultant product was extracted with ethyl acetate
  3. washThe organic layer was washed with water and brine
  4. customdried
  5. customthe solvent was evaporated under reduced pressure
  6. additionTo a mixture of the obtained residue in toluene (125 mL)
  7. additionwater (7.5 mL) were added dihydroxyphenylborane (5.82 g), potassium carbonate (4.40 g) and tetrakis(triphenylphosphine)palladium(0) (3.67 g)
  8. stirringthe mixture was stirred under an argon atmosphere at 100° C. for 14 hr
  9. additionThe reaction mixture was poured into water
  10. extractionthe resultant product was extracted with ethyl acetate
  11. washThe organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and brine
  12. customdried
  13. customthe solvent was evaporated under reduced pressure
  14. customThe obtained residue was purified by silica gel column chromatography (solvent gradient; 10→20% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-8f0711308b424267b9335123fb1e1b93
Source dataset
uspto-grants-2013_06
Patent number
US08470816B2

Reaction notes

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