反应详情

温度

-78 °C

A solution of freshly prepared lithium diisopropylamide (23 mL of a 0.31M stock solution, 7.13 mmol) cooled to −78° C. was treated with (3-methoxy-phenyl)-acetic acid methyl ester (1.07 g, 5.94 mmol) in tetrahydrofuran/1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (14.8 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 (1.37 g, 6.53 mmol) in 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (1.16 mL). The reaction 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. At this time, the reaction was quenched by the dropwise addition of a saturated aqueous ammonium chloride solution. This solution was diluted with water (100 mL) and extracted into ethyl acetate (3×50 mL). The organics were washed with a saturated aqueous lithium chloride solution (1×75 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 95/5 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-(3-methoxy-phenyl)-propionic acid methyl ester (1.39 g, 89.1%) as a clear oil: EI-HRMS m/e calcd for C16H22O3 (M+) 262.1568, found 262.1561.

1. stirringThe reaction mixture was stirred at −78° C. for 3 h
2. temperatureThe reaction was then warmed to 25° C.
3. stirringwas stirred at 25° C. for 16 h
4. customAt this time, the reaction was quenched by the dropwise addition of a saturated aqueous ammonium chloride solution
5. additionThis solution was diluted with water (100 mL)
6. extractionextracted into ethyl acetate (3×50 mL)
7. washThe organics were washed with a saturated aqueous lithium chloride solution (1×75 mL)
8. dry with materialdried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo