Triethylamine → HCID 54527806, compound

Temperature

5 °C

A mixture of 2-(3-(3-methylphenyl)-3-phenyl-2-propen-1-yloxy)ethanol (16 g, 60 mmol) and triethylamine (15.1 g, 149 mmol) in dry toluene (75 ml) kept under a nitrogen atmosphere was cooled to 5° C. and a solution of methanesulphonyl chloride (13.7 g, 119 mmol) in dry toluene (75 ml) was added dropwise keeping the temperature below 10° C. When addition was complete the reaction mixture was stirred for 1.5 h at 5° C. Water was added (100 ml) and the mixture was stirred at room temperature for 0.5 h. The phases were separated and the aqueous phase was extracted with a small portion of toluene. The combined organic extracts was washed with brine, dried over sodium sulphate and filtered. To the filtrate was added ethyl (R)-3-piperidinecarboxylate (10.3 g, 66 mmol) and potassium carbonate (9.9 g, 72 mmol) and the mixture was heated at reflux temperature for 6 days. Another portion of ethyl (R)-3-piperidinecarboxylate (5.3 g) was added and the mixture was heated at reflux temperature for another 24 h. The reaction mixture was poured into ice water (200 ml) and extracted with ethyl acetate (2×200 ml). The combined organic extracts was washed with a sodium citrate buffer solution (2×100 ml, pH 5) and then extracted with a 5% aqueous citric acid solution (4×100 ml). Toluene (120 ml) was added to the combined acidic extracts and sodium hydroxide pellets was added to the mixture until the pH was measured at 8.5. The phases were separated and the organic phase was dried over sodium sulphate. The solvent was evaporated in vacuo to give 9.4 g (39%) of (R)-N-(2-(3-(3-methylphenyl)-3-phenyl-2-propen-1-yloxy)ethyl)-3-piperidinecarboxylic acid ethyl ester as an oil. TLC: rf=0.50 (SiO2 ; dichloromethane/methanol/acetic acid=20:2:1).

1. customthe temperature below 10° C
2. additionWhen addition
3. stirringthe mixture was stirred at room temperature for 0.5 h
4. customThe phases were separated
5. extractionthe aqueous phase was extracted with a small portion of toluene
6. washThe combined organic extracts was washed with brine
7. dry with materialdried over sodium sulphate
8. filtrationfiltered
9. temperaturethe mixture was heated
10. temperatureat reflux temperature for 6 days
11. temperaturethe mixture was heated
12. temperatureat reflux temperature for another 24 h
13. extractionextracted with ethyl acetate (2×200 ml)
14. washThe combined organic extracts was washed with a sodium citrate buffer solution (2×100 ml, pH 5)
15. extractionextracted with a 5% aqueous citric acid solution (4×100 ml)
16. additionToluene (120 ml) was added to the combined acidic extracts and sodium hydroxide pellets
17. additionwas added to the mixture until the pH
18. customThe phases were separated
19. dry with materialthe organic phase was dried over sodium sulphate
20. customThe solvent was evaporated in vacuo

ORD record

ord-471bcd45e6c74a14a2fb801d9289fde6

Source dataset

uspto-grants-1993_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05198451