4-Toluenesulfonyl chloride → N-(2-(3,3-Diphenyl-1-propyloxy)ethyl)-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid ethyl ester

HRID 1614798Notes

Reaction equation

HRID 1614798 reaction equation
[C:1]1([CH:7]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:8][CH2:9][O:10][CH2:11][CH2:12]O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([Li])CCC.C1(C)C=CC(S(Cl)(=O)=O)=CC=1.Cl.[NH:37]1[CH2:42][CH2:41][CH:40]=[C:39]([C:43]([O:45][CH2:46][CH3:47])=[O:44])[CH2:38]1.C(=O)([O-])[O-].[K+].[K+]>C1COCC1.C(OCC)(=O)C>[CH2:46]([O:45][C:43]([C:39]1[CH2:38][N:37]([CH2:12][CH2:11][O:10][CH2:9][CH2:8][CH:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:42][CH2:41][CH:40]=1)=[O:44])[CH3:47]

Participants

8

Reactant 5

HCID 73974-Toluenesulfonyl chlorideHCID 11430Potassium CarbonateHCID 205700Ethyl 1,2,5,6-tetrahydropyridine-3-carboxylate hydrochlorideHCID 106348432-(3,3-Diphenyl-1-propyloxy)ethanolHCID 178418339Butyllithium

Product 1

HCID 10691978N-(2-(3,3-Diphenyl-1-propyloxy)ethyl)-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid ethyl esterYield 32.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
10 °C

Procedure

A solution of 2-(3,3-diphenyl-1-propyloxy)ethanol (3.9 g, 15 mmol) in dry THF (30 ml) kept under a nitrogen atmosphere was cooled to 10° C. and a solution of n-butyllithium in hexanes (6.0 ml, 2.5 M) was added dropwise. The reaction mixture was stirred for 1 h at room temperature and heated at reflux temperature for 1.5 h and then cooled to room temperature. p-Toluenesulphonyl chloride (2.9 g, 15 mmol) was added and the mixture was stirred at room temperature for 1.5 h. Ethyl 1,2,5,6-tetrahydro-3-pyridinecarboxylate hydrochloride (3.8 g, 20 mmol) and potassium carbonate (5.0 g, 38 mmol) were added and the mixture was stirred at room temperature for 0.5 h and then heated at reflux temperature for 4 h. The reaction mixture was allowed to stand overnight and was diluted with ice water (25 ml) and ethyl acetate (100 ml). The separated organic phase was extracted with a 10% citric acid solution (4×50 ml) and the combined aqueous extracts was washed with ethyl acetate (25 ml). The acidic aqueous phase was adjusted to pH 5 with a sodium bicarbonate solution and extracted with ethyl acetate. The organic extract was washed with a diluted sodium bicarbonate solution, dried over sodium sulphate and the solvent evaporated in vacuo to give 1.9 g (32%) of the title compound as an oil. TLC: rf=0.21 (SiO2 ; n-heptane/THF=7:3). 1H NMR (CDCl3)δ 4.12 (t, 1H); 7.00 (m, 1H).

Workup

  1. temperatureheated
  2. temperatureat reflux temperature for 1.5 h
  3. temperaturecooled to room temperature
  4. stirringthe mixture was stirred at room temperature for 1.5 h
  5. stirringthe mixture was stirred at room temperature for 0.5 h
  6. temperatureheated
  7. temperatureat reflux temperature for 4 h
  8. waitto stand overnight
  9. extractionThe separated organic phase was extracted with a 10% citric acid solution (4×50 ml)
  10. washthe combined aqueous extracts was washed with ethyl acetate (25 ml)
  11. extractionextracted with ethyl acetate
  12. extractionThe organic extract
  13. washwas washed with a diluted sodium bicarbonate solution
  14. dry with materialdried over sodium sulphate
  15. customthe solvent evaporated in vacuo

Sources & evidence

ORD record
ord-ffb2fabc2216474fb639c8d90b4ae750
Source dataset
uspto-grants-1993_03
Patent number
US05198451

Reaction notes

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