Lithium diisopropylamide → 2-(3-Chloro-phenyl)-3-cyclopentyl-propionic acid ethyl ester

Temperatur

-78 °C

A solution of freshly prepared lithium diisopropylamide (23 mL of 0.31 M stock solution, 7.13 mmol) cooled to −78° C. was treated with (3-chloro-phenyl)-acetic acid ethyl ester (1.28 g, 6.48 mmol) in tetrahydrofuran/hexamethylphosphoramide (16.1 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 iodomethylcyclopentane (1.50 g, 7.13 mmol) in hexamethylphosphoramide (1 mL). The reaction mixture was stirred at −78° C. for 4 h. The reaction was warmed to 25° C. and 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). This mixture was poured into water (100 mL) and extracted with ethyl acetate (3×50 mL). The organics were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 75/25 hexanes/ethyl acetate) afforded 2-(3-chloro-phenyl)-3-cyclopentyl-propionic acid ethyl ester (1.70 g, 93%) as a yellow oil: EI-HRMS m/e calcd for C16H21ClO2 (M+) 280.1230, found 280.1238.

1. stirringThe reaction mixture was stirred at −78° C. for 4 h
2. temperatureThe reaction was warmed to 25° C.
3. stirringstirred at 25° C. for 16 h
4. customThe reaction mixture was then quenched by the dropwise addition of a saturated aqueous ammonium chloride solution (20 mL)
5. additionThis mixture was poured into water (100 mL)
6. extractionextracted with ethyl acetate (3×50 mL)
7. dry with materialThe organics were dried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo

ORD-Eintrag

ord-8c05d5dd047540de9384720b7444c5a7

Quelldatensatz

uspto-grants-2001_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06320050B1