Reaktion #1784940

Reaktionsgleichung

4-Bromo-2-(4-bromo-naphthalen-1-yl)-butyric acid methyl ester

potassium carbonate

(4-Bromo-naphthalen-1-yl)-acetic acid methyl ester

lithiumdiisopropylamide

1,2-dibromoethane

→

title compound

Ausbeute 30.0%

1-(4-Bromo-naphthalen-1-yl)-cyclopropanecarboxylic acid

Ausbeute 30.0%

Lösungsmittel

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran heptane ethylbenzene

Hexamethylphosphoramide

Reaktionsbedingungen

Aufarbeitung

1. 1
   EinengenThe reaction mixture was concentrated under vacuo
2. 2
   Sonstigethe residue partitioned between ethylacetate
3. 3
   ExtraktionThe aqueous layer was extracted with ethyl acetate
4. 4
   Waschenthe combined organic layers were washed with water and brine
5. 5
   Trocknendried over sodium sulfate
6. 6
   Filtrationfiltered
7. 7
   Einengenconcentrated in vacuo
8. 8
   Sonstigeto afford a crude mixture
9. 9
   workup.STIRRINGThe mixture was stirred at room temperature for 36 hr
10. 10
    Einengenconcentrated under vacuo
11. 11
    Sonstigepartitioned between ethyl acetate
12. 12
    ExtraktionThe aqueous layer was extracted with ethyl acetate
13. 13
    Einengenthe combined organic layers were concentrated in vacuo
14. 14
    EinengenThe crude mixture was concentrated to dryness
15. 15
    Sonstigepurified by chromatography on silica gel

Vorschrift

To a solution of (4-Bromo-naphthalen-1-yl)-acetic acid methyl ester (Example 472a), 687 mg) in tetrahydrofuran (13 mL) and Hexamethylphosphoramide (1.3 mL) was added at −78° C. a solution of lithiumdiisopropylamide (2M, 2.71 mL) in tetrahydrofuran/heptane/ethylbenzene within 5 min. 1,2-dibromoethane (695 mg) was added rapidly and the reaction mixture was stirred at room temperature for 3 hr. The reaction mixture was concentrated under vacuo and the residue partitioned between ethylacetate and a saturated aqueous solution of ammonium chloride. The aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with water and brine, dried over sodium sulfate, filtered and concentrated in vacuo to afford a crude mixture containing 4-Bromo-2-(4-bromo-naphthalen-1-yl)-butyric acid methyl ester. This crude material was dissolved in tetrahydrofuran (13 mL) at room temperature and potassium carbonate (692 mg) was added. The mixture was stirred at room temperature for 36 hr, concentrated under vacuo, partitioned between ethyl acetate and a hydrochloric acid (0.1N). The aqueous layer was extracted with ethyl acetate and the combined organic layers were concentrated in vacuo. The crude mixture was concentrated to dryness and purified by chromatography on silica gel to yield the title compound as a colorless oil (215 mg; 30%). MS (ESI): m/z=290 [M−H]−.

Quelle