Carbon Dioxide → HCID 58478757, compound

Temperature

-50 °C

A solution of 2,2,6,6-tetramethyl-piperidine (4.05 ml, 24 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 (8.8 mL of a 2.5 M solution in hexanes, 22 mmol) and the reaction is let stir at −50° C. for 0.5 h. Solid 2-chloro-isonicotinic acid, (1.58 g, 10 mmol) is added as a solid to the reaction mixture at −50° C. The reaction is stirred at −50° C. for 0.5 h. The reaction mixture is treated with paraformaldehyde (7 equivalents) dropwise at −50° C. The reaction is stirred at −50° 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 ˜5 and is then extracted with ether (2×40 mL) The aqueous solution is treated with aqueous 1N HCl solution until the pH ˜2. An oily residue separated which from solution is collected to give the title compound as a yellow oil (0.62 g, 36%).

1. customThe cooled reaction mixture
2. stirringThe reaction is stirred at −50° C. for 0.5 h
3. stirringThe reaction is stirred at −50° C. for 2 h
4. temperaturewarmed to room temperature overnight
5. concentrationThe reaction mixture is concentrated
6. customto remove solvent and water and ether
7. additionare added
8. extractionThe aqueous layer is extracted with ether (6×50 ml)
9. additionThe aqueous phase is treated with aqueous 1N HCl solution, until the pH of aqueous layer
10. extractionis then extracted with ether (2×40 mL) The aqueous solution
11. additionis treated with aqueous 1N HCl solution until the pH ˜2
12. customAn oily residue separated which from solution
13. customis collected

ORD record

ord-070eb8b3742c46478cc8a3bacca55264

Source dataset

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08455535B2