Methanol → 1-Tert-butyl 4-methyl 1,2,3,6-tetrahydropyridine-1,4-dicarboxylate

HRID 1059352Notes

Reaction equation

HRID 1059352 reaction equation
C([N:8]1[CH2:13][CH:12]=[C:11]([C:14]([O:16][CH3:17])=[O:15])[CH2:10][CH2:9]1)C1C=CC=CC=1.ClC(OC(Cl)C)=O.CO.[C:27]([O:34]C([O-])=O)([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=O>ClCCl.C(N(CC)CC)C>[C:30]([O:29][C:27]([N:8]1[CH2:9][CH:10]=[C:11]([C:14]([O:16][CH3:17])=[O:15])[CH2:12][CH2:13]1)=[O:34])([CH3:31])([CH3:32])[CH3:33]

Participants

7

Reactant 4

HCID 887MethanolHCID 5213051-Chloroethyl chloroformateHCID 21764251Methyl 1-Benzyl-1,2,3,6-tetrahydropyridine-4-carboxylateHCID 22064466Tert-butyldicarbonate

Product 1

HCID 118067821-Tert-butyl 4-methyl 1,2,3,6-tetrahydropyridine-1,4-dicarboxylateYield 92.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
70 °C

Procedure

4.62 g of methyl 1-benzyl-1,2,3,6-tetrahydro-4-pyridinecarboxylate was dissolved in 30 ml of dichloromethane. Under ice-cooling, 4.29 g of 1-chloroethyl chloroformate was added thereto and the resulting mixture was heated under reflux for 2 hours. After adding 50 ml of methanol, the mixture was stirred at 70° C. for 1 hour and 20 minutes. Then triethylamine was added to the reaction mixture under ice-cooling until the pH value of the mixture exceeded 7. After further adding 4.37 g of tert-butyl dicarbonate, the resulting mixture was stirred at room temperature for 10 minutes. Then the reaction mixture was concentrated under reduced pressure, diluted with ethyl acetate, washed successively with water and a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate. After filtration, the solvent was distilled off under reduced pressure and the obtained residue was purified by silica gel column chromatography (eluted with n-hexane/ethyl acetate) to thereby give 4.46 g of the title compound as a yellow oily substance.

Workup

  1. temperatureUnder ice-cooling
  2. temperaturethe resulting mixture was heated
  3. temperatureunder reflux for 2 hours
  4. temperaturecooling until the pH value of the mixture
  5. stirringthe resulting mixture was stirred at room temperature for 10 minutes
  6. concentrationThen the reaction mixture was concentrated under reduced pressure
  7. additiondiluted with ethyl acetate
  8. washwashed successively with water
  9. dry with materiala saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate
  10. filtrationAfter filtration
  11. distillationthe solvent was distilled off under reduced pressure
  12. customthe obtained residue was purified by silica gel column chromatography (eluted with n-hexane/ethyl acetate)

Sources & evidence

ORD record
ord-8bf3af294f0b474c8d4c9e10b5def722
Source dataset
uspto-grants-2003_02
Patent number
US06518423B1

Reaction notes

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