3-Chlorophenylacetic acid → 2-(3-Chlorophenyl)-1-(5-chloropyridin-2-yl)ethanone

Temperatur

-78 °C

To a solution of 3-chlorophenylacetic acid (326.5 g, 1.91 mol, 0.95 eq) in THF (1.82 L) at −78° C. was slowly added NaHMDS (1M solution in THF, 3.82 L, 3.82 mol, 2 eq) over 2 h 45 min while keeping the temperature below −65° C. After the addition was complete, the reaction mixture was stirred for 30 min at −78° C. A solution of methyl 5-chloropicolinate (326.5 g, 1.91 mol, Example 121, Step A) in THF (0.9 L) was added to the above solution at −78° C. over 30 min. The reaction was stirred for another 1 h and then allowed to warm to ambient temperature overnight. The reaction mixture was slowly transferred into a sat. aq. ammonium chloride solution (4 L), extracted with ethyl acetate (2×8 L), and then the combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated. Purification of the residue by flash chromatography on silica gel (eluent: DCM) provided the title compound as a white solid.

1. customat −78° C.
2. customover 2 h
3. custom45 min
4. customthe temperature below −65° C
5. additionAfter the addition
6. stirringThe reaction was stirred for another 1 h
7. temperatureto warm to ambient temperature overnight
8. extractionextracted with ethyl acetate (2×8 L)
9. dry with materialthe combined organic layers were dried over Na2SO4
10. filtrationfiltered
11. concentrationthe filtrate was concentrated
12. customPurification of the residue by flash chromatography on silica gel (eluent: DCM)

ORD-Eintrag

ord-8ff85211339447779bde73ffd017e776

Quelldatensatz

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09296736B2