Potassium Carbonate → Ethyl 4-oxobutanoate

Temperatur

80 °C

A mixture of 4-[4-(3-chloro-propoxy)-phenyl]-3-methyl-4-oxo-butyric acid ethyl ester (7 g, 22 mmol), K2CO3 (9.3 g, 67 mmol), Nat (330 mg, 2.2 mmol), and (R)-methyl-pyrrolidinium benzenesulfonate (11 g, 47 mmol) in CH3CN (160 mL) was heated under argon at 80° C. for 36 h. The reaction mixture was concentrated at reduced pressure and partitioned between saturated aqueous sodium bicarbonate solution and methylene chloride. The aqueous layer was extracted twice with methylene chloride and the combined organics was washed with brine, dried (Na2SO4), filtered, and concentrated to provide a crude material. The crude material was purified by ISCO (80 g siliga gel column) chromatography using 2% to 9% methanol in methylene chloride to 10% methanol containing 2.5 mL ammonium hydroxide in methylene chloride to afford a pure product. The pure product was dissolved in methylene chloride and washed with saturated aqueous sodium bicarbonate solution, brine, dried (Na2SO4), filtered, and concentrated to give 3-methyl-4-{4-R-2-methyl-pyrrolidin-1-yl)-propoxy]-phenyl}-4-oxo-butyric acid ethyl ester (8.39 g, quantitative yield), MS m/z 362 (M+H).

1. concentrationThe reaction mixture was concentrated at reduced pressure
2. custompartitioned between saturated aqueous sodium bicarbonate solution and methylene chloride
3. extractionThe aqueous layer was extracted twice with methylene chloride
4. washthe combined organics was washed with brine
5. dry with materialdried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated
8. customto provide a crude material
9. customThe crude material was purified by ISCO (80 g siliga gel column) chromatography
10. customto afford a pure product
11. washwashed with saturated aqueous sodium bicarbonate solution, brine
12. dry with materialdried (Na2SO4)
13. filtrationfiltered
14. concentrationconcentrated

ORD-Eintrag

ord-3f08e34100324d4fae84cc8d9e600134

Quelldatensatz

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08207168B2