Dimethylformamide → 1-Phenylmethyl-alpha,alpha-dimethyl-1,2,3,6-tetrahydro-4-pyridine-acetic acid ethyl ester

HRID 1691851Notes

Reaction equation

HRID 1691851 reaction equation
[CH2:1]([O:3][C:4](=[O:22])[C:5]([C:8]1(O)[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)([CH3:7])[CH3:6])[CH3:2].CN(C)C=O.S(Cl)(Cl)=O>C(Cl)(Cl)Cl>[CH2:1]([O:3][C:4](=[O:22])[C:5]([C:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:10][CH:9]=1)([CH3:7])[CH3:6])[CH3:2]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 542124921-phenylmethyl-alpha,alpha-dimethyl-4-hydroxy-4-piperidine-acetic Acid Ethyl Ester

Product 1

HCID 545483681-Phenylmethyl-alpha,alpha-dimethyl-1,2,3,6-tetrahydro-4-pyridine-acetic acid ethyl esterYield 38.4%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

2-(1-benzyl-4-hydroxy-piperidin-4-yl)-2-methyl-propionic acid ethyl ester (3.24 g, 10.6 mmol) from above was dissolved in chloroform (13 mL) containing N,N-dimethylformamide (34 μL). To this solution was added thionyl chloride (1.56 mL). The mixture was refluxed overnight. Solvents were evaporated and the residue was extracted with ethyl acetate and sodium hydroxide (1N) solution. The organic layer was washed with brine and dried over sodium sulfate. After evaporation of solvents, the residue was purified using flash chromatography (eluting with ethyl acetate and hexanes) to give 2-(1-benzyl-1,2,3,6-tetrahydro-pyridin-4-yl)-2-methyl-propionic acid ethyl ester (1.17 g) as an oily material. The NMR spectrum obtained on the sample is compatible with its structure. LC-MS calcd for C18H25NO2 (m/e) 287.4, obsd 288.2 (M+H).

Workup

  1. temperatureThe mixture was refluxed overnight
  2. customSolvents were evaporated
  3. extractionthe residue was extracted with ethyl acetate and sodium hydroxide (1N) solution
  4. washThe organic layer was washed with brine
  5. dry with materialdried over sodium sulfate
  6. customAfter evaporation of solvents
  7. customthe residue was purified
  8. washflash chromatography (eluting with ethyl acetate and hexanes)

Sources & evidence

ORD record
ord-9e36406dcdca4d598c583d399c106c92
Source dataset
uspto-grants-2012_04
Patent number
US08153644B2

Reaction notes

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