Methanol → 4-(4-fluorophenyl)-N-methylbutyramide

Temperatur

0 °C

At 0° C., 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (6.99 g, 36.5 mmol) was added to a solution of crude 4-(4-fluorophenyl)butyric acid (6.64 g, 36.5 mmol) and 1-hydroxybenzotriazole (4.92 g, 36.5 mmol) in N,N-dimethylformamide (50 ml) and DCM (50 ml). The reaction mixture was stirred for 20 min at 0° C. An 8.0 M solution of methylamine in methanol (91 ml. 729 mmol) was added. The reaction mixture was stirred for 16 hours, while it was warming up to room temperature. It was diluted with ethyl acetate (200 ml) and washed with a 10% aqueous solution of sodium hydrogen sulphate (100 ml). The aqueous phase was extracted with ethyl acetate (100 ml). The combined organic layers were washed with a saturated solution of sodium hydrogen carbonate (200 ml) and dried over magnesium sulphate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (100 g), using ethyl acetate/heptane 3:1 as eluent. The product was dissolved in ethyl acetate (200 ml) and washed with water (200 ml). The organic layer was dried over magnesium sulphate. The solvent was removed in vacuo to give 1.31 g of 4-(4-fluorophenyl)-N-methylbutyramide.

1. stirringThe reaction mixture was stirred for 16 hours, while it
2. temperaturewas warming up to room temperature
3. washwashed with a 10% aqueous solution of sodium hydrogen sulphate (100 ml)
4. extractionThe aqueous phase was extracted with ethyl acetate (100 ml)
5. washThe combined organic layers were washed with a saturated solution of sodium hydrogen carbonate (200 ml)
6. dry with materialdried over magnesium sulphate
7. customThe solvent was removed in vacuo
8. customThe crude product was purified by flash chromatography on silica (100 g)
9. dissolutionThe product was dissolved in ethyl acetate (200 ml)
10. washwashed with water (200 ml)
11. dry with materialThe organic layer was dried over magnesium sulphate
12. customThe solvent was removed in vacuo

ORD-Eintrag

ord-e57e45411c2d4325b1157e3d4ad7564c

Quelldatensatz

uspto-grants-2002_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06437147B1