1-Methoxy-1-trimethylsilyloxypropene → Methyl 2-(6-chloro-2-methoxypyridin-3-yl)propanoate

Temperatur

85 °C

To a dry flask was added 3-bromo-6-chloro-2-methoxypyridine (9.7 g, 43.7 mmol), palladium(0)bis(dibenzylideneacetone) (1.3 g, 2.2 mmol), and zinc fluoride (3.4 g, 32.7 mmol). The mixture was degassed with nitrogen. A solution of tri-tert-butylphoshine/toluene (1.0 M, 4.4 mL, 4.4 mmol) in DMF (146 mL) was then added to the degassed mixture. After stirring, (E)-(1-methoxyprop-1-enyloxy)trimethylsilane (15.2 mL, 65 mmol) was added and the reaction was heated at 85° C. for 18 h. The mixture was partitioned between MTBE and brine. The aqueous layer was extracted with MTBE. The combined organic layers were dried over Na2SO4 and concentrated. Purification by silica gel column chromatography (330 g RediSep Gold column, 30-65% DCM/heptanes) provided methyl 2-(6-chloro-2-methoxypyridin-3-yl)propanoate (6.4 g, 64%); 1H NMR (600 MHz, CDCl3) δ: 1.44 (d, 3H), 3.67 (s, 3H), 3.91 (q, 1H), 3.95 (s, 3H), 6.89 (d, 1H), 7.45 (d, 1H).

1. customThe mixture was degassed with nitrogen
2. customThe mixture was partitioned between MTBE and brine
3. extractionThe aqueous layer was extracted with MTBE
4. dry with materialThe combined organic layers were dried over Na2SO4
5. concentrationconcentrated
6. customPurification by silica gel column chromatography (330 g RediSep Gold column, 30-65% DCM/heptanes)

ORD-Eintrag

ord-e8e07004844e4b09aedabc9266e5beff

Quelldatensatz

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09278953B2