Methyl 2-(3-nitrophenyl)acetate → 3-Cyclopentyl-2-(3-nitro-phenyl)-propionic acid methyl ester

Temperatur

-78 °C

A solution of freshly prepared lithium diisopropylamide (43.3 mL of a 0.3M stock solution, 12.99 mmol) cooled to −78° C. was treated with (3-nitro-phenyl)-acetic acid methyl ester (2.45 g, 12.56 mmol) in tetrahydrofuran/1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (32 mL, 3:1). The resulting solution was stirred at −78° C. for 45 min. Iodomethylcyclopentane (2.78 g, 13.23 mmol) was then added in 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (2.78 mL), and the mixture was stirred at −78° C. for 3 h. The reaction was 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 (25 mL) and was concentrated in vacuo. The residue was diluted with water (50 mL) and extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with a saturated aqueous lithium chloride solution (2×25 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh 80/20 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-(3-nitro-phenyl)-propionic acid methyl ester (1.63 g, 46.8%) as pale yellow oil: EI-HRMS m/e calcd for C15H19NO4 (M+) 277.1314, found 277.1317.

1. stirringthe mixture was stirred at −78° C. for 3 h
2. temperatureThe reaction was warmed to 25° C.
3. stirringwas stirred at 25° C. for 16 h
4. customThe reaction mixture was then quenched by the dropwise addition of a saturated aqueous ammonium chloride solution (25 mL)
5. concentrationwas concentrated in vacuo
6. additionThe residue was diluted with water (50 mL)
7. extractionextracted with ethyl acetate (3×50 mL)
8. washThe combined organic layers were washed with a saturated aqueous lithium chloride solution (2×25 mL)
9. dry with materialdried over sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated in vacuo

ORD-Eintrag

ord-ba25baa5b6164294af089f38fd1a1aa8

Quelldatensatz

uspto-grants-2003_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06610846B1