반응 #494437

반응 방정식

Methyl 4-amino-6-(4-chloro-3-fluorophenyl)-5-fluoro-3-iodopicolinate

tri-n-butylmethylthiostannane

water

stannane

→

written product

수율 76.2%

Methyl 4-amino-6-(4-chloro-3-fluorophenyl)-5-fluoro-3-(methylthio)picolinate

수율 76.2%

용매

DMF

ethyl acetate

반응 조건

후처리

1. 1
   기타The solution was purged with a nitrogen stream for 10 m
2. 2
   온도heating
3. 3
   workup.WAITwas continued for 8 h
4. 4
   온도After cooling
5. 5
   여과filtered through a glass wool plug
6. 6
   기타to remove yellow solids
7. 7
   기타The organic phase was separated
8. 8
   여과After filtration through diatomaceous earth
9. 9
   세척the solution was washed with 10 ml water, 10 ml sat. NaCl
10. 10
    건조dried (Na2SO3)
11. 11
    기타evaporated
12. 12
    기타The crude material was purified by silica gel chromatography
13. 13
    기타After evaporation of the solvents the oily product
14. 14
    workup.STIRRINGwas stirred with hexane
15. 15
    기타to produce a white solid which
16. 16
    여과was collected by filtration
17. 17
    기타dried under vacuum

실험 절차

Methyl 4-amino-6-(4-chloro-3-fluorophenyl)-5-fluoro-3-iodopicolinate (420 mg, 0.99 mmol) and tri-n-butylmethylthiostannane (530 mg, 1.6 mmol) were dissolved in 5 ml dry DMF. The solution was purged with a nitrogen stream for 10 m, treated with his (triphenylphosphine) palladium (II) chloride (70 mg, 0.01 mmol) and copper (I) iodide (19 mg, 0.01 mmol) and heated to 100° C. After 5 h, an additional 350 mg, 1.0 mmol, of the stannane were added and heating was continued for 8 h more. After cooling, the mixture was stirred with 10 ml water and 50 ml ethyl acetate and then filtered through a glass wool plug to remove yellow solids. The organic phase was separated and stirred with 25 ml 10% aq. potassium bifluoride solution for 30 m. After filtration through diatomaceous earth, the solution was washed with 10 ml water, 10 ml sat. NaCl, dried (Na2SO3) and evaporated. The crude material was purified by silica gel chromatography using a 0-40% ethyl acetate-hexane gradient. After evaporation of the solvents the oily product was stirred with hexane to produce a white solid which was collected by filtration and dried under vacuum to give 260 mg of the written product as a white solid: mp 125-126° C.; 1H NMR (400 MHz, CDCl3) δ 7.77 (dd, J=28.9, 9.5 Hz, 2H), 7.47 (m, 1H), 5.28 (s, 2H), 3.99 (s, 3H), 2.35 (s, 3H). 19F NMR (376 MHz, CDCl3) δ −115.10, −143.40; ESIMS m/z 345 ([M+H]+), 343 ([M−H]−).

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