Phosphoric Acid → Methyl 4-(4-chloro-2-fluoro-3-methoxyphenyl)-2-methylnicotinate

温度

100 °C

A mixture of methyl 4-chloro-2-methylnicotinate (1.5 g, 8.08 mmol), 2-(4-chloro-2-fluoro-3-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (2.316 g, 8.08 mmol), phosphoric acid, potassium salt (3.43 g, 16.16 mmol) and PdCl2(dppf)-CH2Cl2 adduct (0.660 g, 0.808 mmol) in 1,4-dioxane (25 mL) and water (5 mL) was purged with nitrogen for 5 min. The reaction was then heated to 100° C. for 18 h. After cooling, the reaction was diluted with water (50 mL) and extracted with ethyl acetate (2×75 mL). The combined organic layers were washed with brine solution, dried over sodium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography using 50% ethyl acetate in hexanes to yield methyl 4-(4-chloro-2-fluoro-3-methoxyphenyl)-2-methylnicotinate (1.2 g, 2.52 mmol, 31% yield) as pale brown oil. LC/MS (ESI) m/e 309.9 [(M+H)+, calcd for C15H14ClFNO3 310.1]; LC/MS retention time (method D): tR=0.84 min.

1. customwas purged with nitrogen for 5 min
2. temperatureAfter cooling
3. additionthe reaction was diluted with water (50 mL)
4. extractionextracted with ethyl acetate (2×75 mL)
5. washThe combined organic layers were washed with brine solution
6. dry with materialdried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residue was purified by silica gel chromatography

ORDレコード

ord-ecca1684e53e4cb092a918d5c103bd5f

出典データセット

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08901305B2