Carbon Dioxide → HCID 58478754, compound

Temperature

-50 °C

A solution of 2,2,6,6-tetramethyl-piperidine (5 ml, 30 mmol) in a 100 ml round bottomed flask equipped with a magnetic stirrer, is put under argon atmosphere and 20 ml of dry THF is added. The reaction mixture is cooled to −50° C. by adding a controlled amount of dry ice to an acetone bath. The cooled reaction mixture is treated dropwise with nBuLi solution (16 mL of a 2.5 M solution in hexanes, 40 mmol) and the reaction is let stir at that −50 C for 0.5 h. A solution of 6-chloro-nicotinic acid (1.58 g, 10 mmol) in THF (20 mL) is added dropwise to the reaction at −50° C. The reaction is stirred at −50° C. for 1.5 h and then cooled to −78° C. The reaction mixture is treated with propionaldehyde (4.2 ml, 58 mmol) dropwise at −50° C. The reaction is stirred at −78° C. for 2 h and warmed to room temperature overnight. The reaction mixture is concentrated to remove solvent and water and ether are added. The aqueous layer is extracted with ether (6×50 ml). The aqueous phase is treated with aqueous 1N HCl solution, until the pH of aqueous layer is ˜6 and is then extracted with ether (3×40 mL). The aqueous solution is treated with aqueous 1N HCl solution until the pH ˜2 and solution is heated at 100° C. overnight. An oily residue separates from solution. Dichloromethane is added to the aqueous phase which dissolves the oily residue. Without extracting, the solution is poured into a separatory funnel and the organic phase is collected. The organic phase is washed with saturated aqueous NaHCO3 solution, dried over Na2SO4, filtered and concentrated to give the title compound (1.45 g, 73%) as a yellow oil.

1. customThe cooled reaction mixture
2. stirringThe reaction is stirred at −50° C. for 1.5 h
3. temperaturecooled to −78° C
4. stirringThe reaction is stirred at −78° C. for 2 h
5. temperaturewarmed to room temperature overnight
6. concentrationThe reaction mixture is concentrated
7. customto remove solvent and water and ether
8. additionare added
9. extractionThe aqueous layer is extracted with ether (6×50 ml)
10. additionThe aqueous phase is treated with aqueous 1N HCl solution, until the pH of aqueous layer
11. extractionis then extracted with ether (3×40 mL)
12. additionThe aqueous solution is treated with aqueous 1N HCl solution until the pH ˜2 and solution
13. temperatureis heated at 100° C. overnight
14. additionDichloromethane is added to the aqueous phase which
15. dissolutiondissolves the oily residue
16. extractionWithout extracting
17. additionthe solution is poured into a separatory funnel
18. customthe organic phase is collected
19. washThe organic phase is washed with saturated aqueous NaHCO3 solution
20. dry with materialdried over Na2SO4
21. filtrationfiltered
22. concentrationconcentrated

ORD record

ord-ba035f3fa4f945ff9db9e84cc4ded9b8

Source dataset

uspto-grants-2011_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07977351B2