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

Temperature

10 °C

2-(3,3-Diphenyl-3-propen-1-yloxy)ethanol (4.0 g, 15.7 mmol) was dissolved in dry dioxan (80 ml) and stirred under an atmosphere of hydrogen for 3 h at room temperature in the presence of 10% palladium on carbon catalyst (50% aqueous paste) and then filtered. The solvent was evaporated in vacuo to give 4.0 g (100%) of 2-(3,3-diphenyl-1-propyloxy)ethanol. 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-butyl-lithium 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 (Na2SO4) and the solvent evaporated in vacuo to give 1.9 9 (32%) of the title compound as an oil.

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 (Na2SO4)
15. customthe solvent evaporated in vacuo

ORD record

ord-8b44643e052c4308b8d9b0c5107a297d

Source dataset

uspto-grants-2001_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06174898B1