Реакция #1947336

Уравнение реакции

(4-chloro-phenyl)-acetic acid ethyl ester

lithium diisopropylamide

1-bromo-2-methyl-propane

→

2-(4-chloro-phenyl)-4-methyl-pentanoic acid ethyl ester

Выход 87.2%

Растворители

tetrahydrofuran hexamethylphosphoramide

hexamethylphosphoramide

Условия реакции

Обработка

1. 1
   workup.STIRRINGThe mixture was stirred at −78° C. for 3 h
2. 2
   ТемператураThe reaction was then warmed to 25° C.
3. 3
   workup.STIRRINGwas stirred at 25° C. for 16 h
4. 4
   ДругоеThe reaction mixture was then quenched by the dropwise addition of a saturated aqueous ammonium chloride solution (20 mL)
5. 5
   workup.ADDITIONThe reaction mixture was poured into water (100 mL)
6. 6
   Экстракцияextracted with ethyl acetate (3×50 mL)
7. 7
   СушкаThe organics layers dried over sodium sulfate
8. 8
   Фильтрацияfiltered
9. 9
   Концентрированиеconcentrated in vacuo

Методика

A solution of freshly prepared lithium diisopropylamide (21.2 mL of a 0.31 M stock solution, 6.14 mmol) cooled to −78° C. was treated with (4-chloro-phenyl)-acetic acid ethyl ester (1.11 g, 5.58 mmol) in tetrahydrofuran/hexamethylphosphoramide (13.9 mL, 3:1). The resulting solution was stirred at −78° C. for 45 min. At this time, the reaction was treated with a solution of 1-bromo-2-methyl-propane (1.81 mL, 16.7 mmol) in hexamethylphosphoramide (1 mL). The mixture was stirred at −78° C. for 3 h. The reaction was then warmed to 25° C. and was stirred at 25° C. for 16 h. The reaction mixture was then quenched by the dropwise addition of a saturated aqueous ammonium chloride solution (20 mL). The reaction mixture was poured into water (100 mL) and extracted with ethyl acetate (3×50 mL). The organics layers dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 50/50 hexanes/ethyl acetate) afforded 2-(4-chloro-phenyl)-4-methyl-pentanoic acid ethyl ester (1.24 g, 87.1%) as a white solid: mp 34-35° C.; EI-HRMS m/e calcd for C14H19ClO2 (M+) 254.1074, found 254.1069.

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