Реакция #308688

Уравнение реакции

3-Trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-1,7-dicarboxylic acid 7-tert-butyl ester

3-trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-1,7-dicarboxylic acid 7-tert-butyl ester

hydrochloric acid

iodomethane

ammonium chloride

tetramethyl-ethylenediamine

n-Butyllithium

→

8-methyl-3-trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-1,7-dicarboxylic acid 7-tert-butyl ester

Выход 24.3%

Растворители

toluene

tetrahydrofuran

water

Условия реакции

Обработка

1. 1
   ДругоеThe reaction flask was placed in a dry ice-acetone bath
2. 2
   ДругоеThe reaction mixture was reacted at −78° C. for 10 minutes
3. 3
   Температураto warm up to room temperature
4. 4
   Другоеreacted for 2 hours
5. 5
   Экстракцияextracted with ethyl acetate (30 mL×3)
6. 6
   СушкаThe combined organic phase was dried over anhydrous sodium sulfate
7. 7
   Фильтрацияfiltered
8. 8
   Концентрированиеconcentrated under reduced pressure
9. 9
   ДругоеThe resulting residue was purified by silica gel column chromatography

Методика

3-Trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-1,7-dicarboxylic acid 7-tert-butyl ester 27d (0.85 g, 2.54 mmol) was dissolved in a mixture of 25 mL of anhydrous toluene and 8 mL of anhydrous tetrahydrofuran. The reaction flask was placed in a dry ice-acetone bath and cooled to −78° C., and then tetramethyl-ethylenediamine (1.32 mL, 8087 mmol) was added to the flask. n-Butyllithium (5.55 mL, 8.87 mmol) was added dropwise in 5 minutes. After reacting at −78° C. for 15 minutes, iodomethane (0.4 mL, 6.34 mmol) was added dropwise. The reaction mixture was reacted at −78° C. for 10 minutes, then was allowed to warm up to room temperature and reacted for 2 hours until thin lay chromatography showed the starting material disappeared. 15 mL of saturated ammonium chloride and 20 mL of water were added to the reaction mixture successively. The mixture was adjusted to pH 3-4 with 2 N hydrochloric acid, and extracted with ethyl acetate (30 mL×3). The combined organic phase was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound 8-methyl-3-trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-1,7-dicarboxylic acid 7-tert-butyl ester 39a (0.215 g, yield 24.3%) as a white solid.

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