1-Chloroethyl chloroformate → HCID 57889620, compound

HRID 1820241Notes

Reaction equation

HRID 1820241 reaction equation
C([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=2)[C:10]([CH3:22])([CH3:21])[CH2:9]1)C1C=CC=CC=1.ClC(OC(Cl)C)=O>ClC(Cl)C>[Cl:20][C:17]1[CH:18]=[CH:19][C:14]([CH:11]2[CH2:12][CH2:13][NH:8][CH2:9][C:10]2([CH3:22])[CH3:21])=[CH:15][CH:16]=1

Participants

4

Reactant 2

HCID 5213051-Chloroethyl chloroformateHCID 57888892HCID 57888892, compound

Product 1

HCID 57889620HCID 57889620, compoundYield 71.4%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

A solution of 1-benzyl-4-(4-chlorophenyl)-3,3-dimethylpiperidine (4.8 g, 15.29 mmol) and 1-chloroethyl chloroformate (1.667 mL, 15.45 mmol) in dichloroethane (40 mL) was stirred overnight at room temperature, then refluxed for 3 hours. The solution was concentrated in-vacuo. The residue was taken up in methanol (50 mL), the mixture was refluxed overnight The mixture was diluted with 75 mL of 1 N HCl, and the methanol was removed under vacuum. The aqueous solution was washed 3× with diethyl ether (20 mL), and the mixture was treated with the careful addition of saturated sodium bicarbonate to reach pH 8. The aqueous solution was washed 3× with diethyl ether (25 mL), and the mixture was treated with the careful addition of solid sodium hydroxide to reach pH>13. The aqueous phase was extracted 3× with ethyl acetate (50 mL), and the combined organic phases were dried over sodium sulfate and concentrated in vacuo to yield (±)-4-(4-chlorophenyl)-3,3-dimethylpiperidine (2.44 g, 10.91 mmol, 71.3% yield) as a pale yellow oil which solidified upon standing. MS: (ESI+)=224.3, (M+H)+. The enantiomers were separated via chiral super-critical fluid chromatography to yield 1.09 g of isomer A, and 1.05 g of isomer B.

Workup

  1. temperaturerefluxed for 3 hours
  2. concentrationThe solution was concentrated in-vacuo
  3. temperaturethe mixture was refluxed overnight The mixture
  4. additionwas diluted with 75 mL of 1 N HCl
  5. customthe methanol was removed under vacuum
  6. washThe aqueous solution was washed 3× with diethyl ether (20 mL)
  7. additionthe mixture was treated with the careful addition of saturated sodium bicarbonate
  8. washThe aqueous solution was washed 3× with diethyl ether (25 mL)
  9. additionthe mixture was treated with the careful addition of solid sodium hydroxide
  10. extractionThe aqueous phase was extracted 3× with ethyl acetate (50 mL)
  11. dry with materialthe combined organic phases were dried over sodium sulfate
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-53afb4d47da6434aa1638a67c6d7115d
Source dataset
uspto-grants-2009_10
Patent number
US07601844B2

Reaction notes

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