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

温度

-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レコード

ord-4e103d0f10ac46deb37e608d5bcb983d

出典データセット

uspto-grants-2010_12

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07851638B2