Dimethylformamide → 1-Benzyl-4-chloro-5,5-dimethyl-1,2,5,6-tetrahydropyridine-3-carbaldehyde

HRID 468668Notes

Reaction equation

HRID 468668 reaction equation
CN([CH:4]=[O:5])C.O=P(Cl)(Cl)[Cl:8].[CH2:11]([N:18]1[CH2:23][CH2:22][C:21](=O)[C:20]([CH3:26])([CH3:25])[CH2:19]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C([O-])(=O)C.[Na+]>C(Cl)Cl>[CH2:11]([N:18]1[CH2:19][C:20]([CH3:26])([CH3:25])[C:21]([Cl:8])=[C:22]([CH:4]=[O:5])[CH2:23]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 517045Sodium AcetateHCID 97944131-Benzyl-3,3-dimethylpiperidin-4-one

Product 1

HCID 866513211-Benzyl-4-chloro-5,5-dimethyl-1,2,5,6-tetrahydropyridine-3-carbaldehydeYield 81.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent4×

Procedure

A solution of anhydrous DMF (142 mL, 1.85 mol) in anhydrous DCM (670 mL) was cooled to 0° C. A solution of POCl3 (121 mL, 1.3 mol) in anhydrous DCM (87 mL) was added dropwise. Upon complete addition, the solution was warmed to room temperature and further to reflux for 30 minutes. A solution of 1-benzyl-3,3-dimethylpiperidin-4-one (75 g, 0.35 mol) in anhydrous DCM (133 mL) was added all at once to the boiling solution and the mixture was further refluxed overnight. The reaction was cooled to room temperature and added dropwise to a biphasic mixture of 4.0 M aqueous sodium acetate (1000 mL) and DCM (300 mL). Upon separation of the layers, the organic layer was washed with water, dried over anhydrous Na2SO4 and concentrated to dryness to afford 1-benzyl-4-chloro-5,5-dimethyl-1,2,5,6-tetrahydropyridine-3-carbaldehyde (75 g, 82% crude yield).

Workup

  1. additionUpon complete addition
  2. temperaturefurther to reflux for 30 minutes
  3. temperaturethe mixture was further refluxed overnight
  4. temperatureThe reaction was cooled to room temperature
  5. customUpon separation of the layers
  6. washthe organic layer was washed with water
  7. dry with materialdried over anhydrous Na2SO4
  8. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-9e1f35683ef3479a92f2b1bdf2fa236c
Source dataset
uspto-grants-2014_01
Patent number
US08624040B2

Reaction notes

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