Реакция #1749393

Уравнение реакции

4-bromo-2-trifluoromethylpyridine

t-butyllithium

(E)-N-((3-bromo-4-methoxyphenyl)(2-cyano-3-fluorophenyl)methylene)-2-methylpropane-2-sulfinamide

Hydrochloric acid

methanol

→

title compound

Выход 89.3%

1-(3-Bromo-4-methoxyphenyl)-4-fluoro-1-(2-(trifluoromethyl)pyridin-4-yl)-1H-isoindol-3-amine

Выход 89.3%

Растворители

THF

THF

THF

Условия реакции

Обработка

1. 1
   workup.WAITThe reaction mixture was left on a thawing
2. 2
   Температураcooling bath for 1 hour
3. 3
   Другоеto reach room temperature
4. 4
   workup.STIRRINGthe reaction was stirred for 1 hour
5. 5
   workup.ADDITIONSilica powder was added
6. 6
   Концентрированиеthe mixture was concentrated under reduced pressure
7. 7
   ДругоеThe residue was purified by flash column chromatography (0-10% 0.1M NH3 in methanol in DCM)

Методика

A solution of 4-bromo-2-trifluoromethylpyridine (1.76 g, 7.80 mmol) in THF (2 mL) was added dropwise at −100° C. to t-butyllithium (9.17 mL, 15.59 mmol) in THF (15 mL) followed by the addition of (E)-N-((3-bromo-4-methoxyphenyl)(2-cyano-3-fluorophenyl)methylene)-2-methylpropane-2-sulfinamide (3.1 g, 7.09 mmol) in THF (10 mL). The reaction mixture was left on a thawing cooling bath for 1 hour and then allowed to reach room temperature and stirred for 2.5 hours. Hydrochloric acid in methanol (1.25 M, 28.4 mL, 35.4 mmol) was added and the reaction was stirred for 1 hour. Silica powder was added and the mixture was concentrated under reduced pressure. The residue was purified by flash column chromatography (0-10% 0.1M NH3 in methanol in DCM) to afford the title compound (3.04 g, 89%).

Источник