1-Chloroethyl chloroformate → tert-Butyl 4-(2-ethoxy-2-oxoethylidene)piperidine-1-carboxylate

HRID 1059355Notes

Reaction equation

HRID 1059355 reaction equation
C([N:8]1[CH2:13][CH2:12][C:11](=[CH:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:10][CH2:9]1)C1C=CC=CC=1.ClC(OC(Cl)C)=O.[C:27]([O:34]C([O-])=O)([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=O>ClC(Cl)C.CO.C(N(CC)CC)C>[C:30]([O:29][C:27]([N:8]1[CH2:13][CH2:12][C:11](=[CH:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:10][CH2:9]1)=[O:34])([CH3:31])([CH3:32])[CH3:33]

Participants

7

Reactant 3

HCID 5213051-Chloroethyl chloroformateHCID 10377866Ethyl 2-(1-benzylpiperidin-4-ylidene)acetateHCID 22064466Tert-butyldicarbonate

Product 1

HCID 10333298tert-Butyl 4-(2-ethoxy-2-oxoethylidene)piperidine-1-carboxylateYield 28.7%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 63651,1-DichloroethaneSolventHCID 8471TriethylamineSolvent

Procedure

51.0 g of ethyl (1-benzylpiperidin-4-ylidene)acetate was dissolved in 200 ml of dichloroethane. After adding 36.5 g of 1-chloroethyl chloroformate under ice-cooling, the resulting mixture was heated under reflux for 2 hours. After adding 100 ml of methanol, the resulting mixture was further heated under reflux for 40 minutes and then allowed to stand at room temperature overnight. Then 60 g of triethylamine was added to the reaction mixture under ice-cooling. Further, 300 ml of methanol was added thereto and the system was made homogeneous. Next, 47.2 g of tert-butyl dicarbonate was added and the resulting mixture was stirred at room temperature for 20 minutes. The reaction mixture was concentrated under reduced pressure, diluted with ethyl acetate, washed successively with 1 N hydrochloric acid, water, a saturated aqueous solution of sodium chloride and saturated sodium hydrogencarbonate and dried over anhydrous magnesium sulfate followed by filtration. After distilling off the solvent under reduced pressure, the crude crystals thus obtained were ground and washed with hexane to thereby give 15.2 g of the title compound. The filtrate was concentrated and the residue was purified by silica gel column chromatography (eluted with n-hexane/ethyl acetate) to thereby give 37.8 g of the additional title compound as colorless crystals.

Workup

  1. temperaturecooling
  2. temperaturethe resulting mixture was heated
  3. temperatureunder reflux for 2 hours
  4. temperaturethe resulting mixture was further heated
  5. temperatureunder reflux for 40 minutes
  6. temperaturecooling
  7. concentrationThe reaction mixture was concentrated under reduced pressure
  8. additiondiluted with ethyl acetate
  9. washwashed successively with 1 N hydrochloric acid, water
  10. dry with materiala saturated aqueous solution of sodium chloride and saturated sodium hydrogencarbonate and dried over anhydrous magnesium sulfate
  11. filtrationfollowed by filtration
  12. distillationAfter distilling off the solvent under reduced pressure
  13. customthe crude crystals thus obtained
  14. washwashed with hexane

Sources & evidence

ORD record
ord-5c4f1371bcc047bfba1e64691b6249b6
Source dataset
uspto-grants-2003_02
Patent number
US06518423B1

Reaction notes

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