Reaktion #485808

Reaktionsgleichung

(3,4-dimethoxy-phenyl)-acetic acid

lithium diisopropylamide

iodomethylcyclopentane

→

3-cyclopentyl-2-(3,4-dimethoxy-phenyl)-propionic acid

Ausbeute 63.9%

Lösungsmittel

tetrahydrofuran 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone

1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturAt this time, the reaction was cooled to 0° C.
2. 2
   workup.STIRRINGThe reaction mixture was stirred at 0° C. for 30 min
3. 3
   TemperaturThe reaction was then warmed to 25° C.
4. 4
   workup.STIRRINGwas stirred at 25° C. for 18 h
5. 5
   SonstigeThe reaction mixture was then quenched by the dropwise addition of saturated aqueous ammonium chloride solution (10 mL)
6. 6
   EinengenThe resulting mixture was concentrated in vacuo
7. 7
   workup.ADDITIONThe residue was diluted with water (100 mL)
8. 8
   ExtraktionThis solution was extracted with ethyl acetate (3×50 mL)
9. 9
   WaschenThe combined organic layers were washed with a saturated aqueous lithium chloride solution (1×100 mL)
10. 10
    Trocknendried over sodium sulfate
11. 11
    Filtrationfiltered
12. 12
    Einengenconcentrated in vacuo

Vorschrift

A solution of freshly prepared lithium diisopropylamide (58.5 mL of a 0.91M stock solution, 53.2 mmol) cooled to −78° C. was treated with (3,4-dimethoxy-phenyl)-acetic acid (4.97 g, 25.3 mmol) in tetrahydrofuran/1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (25.3 mL, 3:1). The resulting solution was stirred at −78° C. for 45 min and at 25° C. for 15 min. At this time, the reaction was cooled to 0° C. and was treated with a solution of iodomethylcyclopentane (5.87 g, 27.8 mmol) in 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (1 mL). The reaction mixture was stirred at 0° C. for 30 min. The reaction was then warmed to 25° C. and was stirred at 25° C. for 18 h. The reaction mixture was then quenched by the dropwise addition of saturated aqueous ammonium chloride solution (10 mL). The resulting mixture was concentrated in vacuo. The residue was diluted with water (100 mL) and acidified to pH=1 with a 1N aqueous hydrochloric acid solution. This solution was extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with a saturated aqueous lithium chloride solution (1×100 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 70/30 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-(3,4-dimethoxy-phenyl)-propionic acid (4.5 g, 63.8%) as a yellow solid: mp 111-112° C.; EI-HRMS m/e calcd for C16H22O4 (M+) 278.1518 found 278.1517.

Quelle