Methyl Tributylstannyl Sulfide → Methyl 4-amino-6-chloro-5-fluoro-3-(methylthio)picolinate

Temperatur

80 °C

Methyl 4-amino-6-chloro-5-fluoro-3-iodopicolinate (1.5 g, 4.6 mmol), tri-n-butylmethylthiostannane (2.5 g, 7.3 mmol), his (triphenylphosphine) palladium (II) chloride (320 mg, 0.46 mmol) and copper (I) iodide (90 mg, 0.46 mmol) were combined 15 ml dry, deaerated DMF and heated to 80° C. After 3 h another 2.5 g portion of the stannane were added and heating was continued for 18 h. After cooling, the mixture was stirred with 25 ml 10% potassium bifluoride solution for 20 ml. The heterogeneous mixture was stirred with 100 ml ethyl acetate and filtered through diatomaceous earth to remove curdy solids. The separated organic phase was washed twice with 15 ml water, 15 ml sat. NaCl, dried (Na2SO3) and evaporated. The product was purified by silica gel chromatography eluting with a 0-25% ethyl acetate-DCM gradient. The gummy residue was stirred with hexane to produce the written product as a white solid, 800 mg. Mp: 75-77° C. 1H NMR (400 MHz, CDCl3) δ 5.35 (s, 2H), 3.96 (s, 3H), 2.33 (s, 3H). 19F NMR (376 MHz, CDCl3) δ −138.81. EIMS m/z 250.

1. customdry
2. additionAfter 3 h another 2.5 g portion of the stannane were added
3. temperatureheating
4. temperatureAfter cooling
5. stirringThe heterogeneous mixture was stirred with 100 ml ethyl acetate
6. filtrationfiltered through diatomaceous earth
7. customto remove curdy solids
8. washThe separated organic phase was washed twice with 15 ml water, 15 ml sat. NaCl
9. dry with materialdried (Na2SO3)
10. customevaporated
11. customThe product was purified by silica gel chromatography
12. washeluting with a 0-25% ethyl acetate-DCM gradient
13. stirringThe gummy residue was stirred with hexane

ORD-Eintrag

ord-6db71d26e3b54614ae953f66ae2e9360

Quelldatensatz

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08754229B2