Triethylamine → HCID 53674309, compound

Temperature

5 °C

A mixture of 2-(3-(3-chlorophenyl)-3-phenyl-2-propen-1-yloxy)ethanol (52.2 g, 0.18 mol) and triethylamine (45.7 g, 0.45 mol) in dry toluene (200 ml) kept under a nitrogen atmosphere was cooled to 5° C. and a solution of methanesulphonyl chloride (41.4 g, 0.36 mol) in dry toluene (200 ml) was added dropwise keeping the temperature below 10° C. When addition was complete the reaction mixture was stirred for 1 h at 5° C. Water was added (250 ml) and the mixture was stirred at room temperature for 10 minutes. The phases were separated and the aqueous phase was extracted with a small portion of toluene. The combined organic extracts were washed with brine and dried (Na2SO4). The mixture was filtered and the filtrate was reduced in vacuo to approximately 500 ml. Ethyl (R)-3-piperidinecarboxylate (56.8 g, 0.36 mol) and potassium carbonate (49.9 g, 0.36 mol) were added and the mixture was heated at reflux temperature for 7 days. The cooled reaction mixture was poured into water (200 ml) and extracted with ethyl acetate (2×200 ml). The combined organic extracts were washed with a sodium citrate buffer solution (pH 5) and then extracted with a 34% aqueous tartaric acid solution (3×100 ml). The combined acidic aqueous extracts were poured into a mixture of ice water (3 l) and ethyl acetate (400 ml). Sodium hydroxide pellets (27.2 g) was added until pH was measured at ca. 4 and the phases were separated. The organic phase was washed with a 5% sodium bicarbonate solution (3×150 ml) and dried (Na2SO4). The solvent was evaporated in vacuo to give 57.5 g (74%) of (R)-N-(2-(3-(3-chloro-phenyl)-3-phenyl-2-propen-1-yloxy)ethyl)-3-piperidinecarboxylic acid ethyl ester as an oil.

1. customthe temperature below 10° C
2. additionWhen addition
3. stirringthe mixture was stirred at room temperature for 10 minutes
4. customThe phases were separated
5. extractionthe aqueous phase was extracted with a small portion of toluene
6. washThe combined organic extracts were washed with brine
7. dry with materialdried (Na2SO4)
8. filtrationThe mixture was filtered
9. temperaturethe mixture was heated
10. temperatureat reflux temperature for 7 days
11. customThe cooled reaction mixture
12. extractionextracted with ethyl acetate (2×200 ml)
13. washThe combined organic extracts were washed with a sodium citrate buffer solution (pH 5)
14. extractionextracted with a 34% aqueous tartaric acid solution (3×100 ml)
15. additionThe combined acidic aqueous extracts were poured into a mixture of ice water (3 l) and ethyl acetate (400 ml)
16. additionwas added until pH
17. customthe phases were separated
18. washThe organic phase was washed with a 5% sodium bicarbonate solution (3×150 ml)
19. dry with materialdried (Na2SO4)
20. customThe solvent was evaporated in vacuo

ORD record

ord-13abb638d2b3418293e870e7bc60c9dd

Source dataset

uspto-grants-2001_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06174898B1