Benzaldehyde → HCID 58478762, compound

Temperature

-50 °C

A solution of 2,2,6,6-tetramethyl-piperidine (7.5 ml, 44 mmol) in a 250 ml round bottomed flask equipped with a magnetic stirrer, is put under argon atmosphere and 30 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 (16.3 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 5,6-dichloro-nicotinic acid, (3.7 g, 18.5 mmol) in THF (15 mL) is added dropwise to the reaction at −50° C. The reaction is stirred at −50° C. for 0.5 h. The reaction mixture is treated with benzaldehyde (2.5 ml, 24 mmol) 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 1N HCl, until the pH of aqueous layer is ˜6 and is then extracted with ether (3×40 mL.) The aqueous solution is treated with 1N HCl solution until the pH ˜2 and solution is heated at 100° C. overnight. On cooling a white precipitate appeared. The precipitate is filtered off and washed with bicarbonate and air-dried to give the title compound (4.6 g, 89%) as a white solid.

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 1N HCl, until the pH of aqueous layer
10. extractionis then extracted with ether (3×40 mL.) The aqueous solution
11. additionis treated with 1N HCl solution until the pH ˜2 and solution
12. temperatureis heated at 100° C. overnight
13. temperatureOn cooling a white precipitate
14. filtrationThe precipitate is filtered off
15. washwashed with bicarbonate
16. customair-dried

ORD record

ord-500c687cd9e0477b95927455b671d315

Source dataset

uspto-grants-2011_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07977351B2