(4-Chlorophenyl)acetic acid → 2-(4-Chloro-phenyl)-3-cyclopentyl-propionic acid

Temperatur

-78 °C

A solution of freshly prepared lithium diisopropylamide (78.0 mL of a 0.91M stock solution, 70.98 mmol) cooled to −78° C. was treated with (4-chloro-phenyl)-acetic acid (5.76 g, 33.8 mmol) in tetrahydrofuran/1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (84 mL, 3:1). The resulting solution was stirred at −78° C. for 1 h. Iodomethylcyclopentane (7.45 g, 35.49 mmol) was then added in 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (2 mL). This solution was stirred at −78° C. for 4 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 excess solvent was removed in vacuo. The residue was acidified to pH=1 with a 1N aqueous hydrochloric acid solution. The mixture was then poured into water (150 mL) and extracted with ethyl acetate (3×50 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 80/20 hexanes/ethyl acetate) afforded 2-(4-chloro-phenyl)-3-cyclopentyl-propionic acid (6.76 g, 79.1%) as a yellow solid: mp 82-84° C.: EI-HRMS m/e calcd for C14H17ClO2 (M+) 252.0917, found 252.0906.

1. stirringThis solution was stirred at −78° C. for 4 h
2. temperatureThe reaction was then 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 (20 mL)
5. customThe excess solvent was removed in vacuo
6. additionThe mixture was then poured into water (150 mL)
7. extractionextracted with ethyl acetate (3×50 mL)
8. dry with materialThe combined organic layers were dried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo

ORD-Eintrag

ord-ba4df412b035424d8af3acfb2593e916

Quelldatensatz

uspto-grants-2003_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06610846B1