Hydrochloric Acid → 4-Chloro-2-(1-cyclopropyl-2-methoxyvinyl)-3-methylpyridine

Temperature

60 °C

A yellow suspension of (4-chloro-3-methylpyridin-2-yl) (cyclopropyl) methanone (2.99 g, 15.28 mmol), (Methoxymethyl) triphenylphosphonium chloride (7.84 g, 22.87 mmol) and Potassium tert-butoxide (3.41 g, 30.4 mmol) in toluene (50 mL) was heated to 60° C. and stirred for 3.5 h. The reaction mixture was cooled down to room temperature and an aqueous solution of 4M Hydrochloric acid (50 mL) was added. The reaction mixture was washed with toluene (3×50 mL). The aqueous layer was diluted in ice, and solid sodium bicarbonate was added until pH reaches 7-8. The mixture was extracted with ethyl acetate (3×100 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtrated and evaporated to dryness. The oily residue was purified by flash column chromatography over silica gel using a gradient of ethyl acetate in heptane to yield a 1 to 1 mixture of the isomeric vinyl ethers as yellow oil (2.93 g, 82%).

1. temperatureThe reaction mixture was cooled down to room temperature
2. washThe reaction mixture was washed with toluene (3×50 mL)
3. additionThe aqueous layer was diluted in ice
4. additionsolid sodium bicarbonate was added until pH
5. extractionThe mixture was extracted with ethyl acetate (3×100 mL)
6. washThe combined organic layers were washed with brine
7. dry with materialdried over sodium sulfate
8. filtrationfiltrated
9. customevaporated to dryness
10. customThe oily residue was purified by flash column chromatography over silica gel using a gradient of ethyl acetate in heptane
11. customto yield a 1

ORD record

ord-b05e5b0705924a74a07d2b04d298de64

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09403818B2