Hexachloroethane → 4-Chloro-2-methoxy-6-(trifluoromethyl)nicotinic acid

Temperature

-50 °C

A solution of LiTMP was formed by cooling a solution of 2,2,6,6-tetramethylpiperidine (862 mg, 6.1 mmol) in THF (5 mL) to −50° C. then adding a solution of n-butyllithium (2.4 mL of 2.5 M in hexanes, 6.1 mmol) dropwise and stirring the mixture for 10 minutes at −50° C. This solution was then cooled to −78 ° C. and a solution of 2-methoxy-6-(trifluoromethyl)nicotinic acid (300 mg, 1.35 mmol) in THF (5 mL) was added dropwise. This mixture was stirred at −78° C. for 2 hours then added via cannula to a pre-cooled solution of hexachloroethane (1.44 g, 6.1 mmol) in THF (5 mL) at −50° C. This mixture was allowed to warm to room temperature over 1 hour then poured into water (20 mL), ethyl acetate (100 mL) added, then washed with hydrochloric acid (2 N, aq, 100 mL). The organic phase was dried over magnesium sulphate, filtered and evaporated to give 4-chloro-2-methoxy-6-(trifluoromethyl)nicotinic acid (312 mg) as an orange solid: 1H NMR (360 MHz, CDCl3): δ 7.36 (1H, s), 4.08 (3H, s).

1. temperatureThis solution was then cooled to −78 ° C.
2. stirringThis mixture was stirred at −78° C. for 2 hours
3. temperatureto warm to room temperature over 1 hour
4. additionadded
5. washwashed with hydrochloric acid (2 N, aq, 100 mL)
6. dry with materialThe organic phase was dried over magnesium sulphate
7. filtrationfiltered
8. customevaporated

ORD record

ord-1e2261420a7e478593030321f9a8f03b

Source dataset

uspto-grants-2009_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07626056B2