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

HRID 407255

反応式

HRID 407255 の反応式
[NH2:1][C:2]1[C:7]([F:8])=[C:6]([C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[C:11]([F:16])[CH:10]=2)[N:5]=[C:4]([C:17]([O:19][CH3:20])=[O:18])[C:3]=1I.C([Sn](CCCC)(CCCC)[S:27][CH3:28])CCC.[SnH4].O>CN(C=O)C.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cu]I.C(OCC)(=O)C>[NH2:1][C:2]1[C:7]([F:8])=[C:6]([C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[C:11]([F:16])[CH:10]=2)[N:5]=[C:4]([C:17]([O:19][CH3:20])=[O:18])[C:3]=1[S:27][CH3:28]

参加物

9

反応物 4

HCID 962WaterHCID 123161StannaneHCID 11110497Methyl Tributylstannyl SulfideHCID 70497132Methyl 4-amino-6-(4-chloro-3-fluorophenyl)-5-fluoro-3-iodopicolinate

生成物 1

HCID 71150700Methyl 4-amino-6-(4-chloro-3-fluorophenyl)-5-fluoro-3-(methylthio)picolinate収率 76.2%

試薬・触媒・溶媒 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 13169693Triphenylphosphine palladium dichloride触媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
100 °C

実験手順

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]−).

後処理

  1. customThe solution was purged with a nitrogen stream for 10 m
  2. temperatureheating
  3. waitwas continued for 8 h
  4. temperatureAfter cooling
  5. filtrationfiltered through a glass wool plug
  6. customto remove yellow solids
  7. customThe organic phase was separated
  8. filtrationAfter filtration through diatomaceous earth
  9. washthe solution was washed with 10 ml water, 10 ml sat. NaCl
  10. dry with materialdried (Na2SO3)
  11. customevaporated
  12. customThe crude material was purified by silica gel chromatography
  13. customAfter evaporation of the solvents the oily product
  14. stirringwas stirred with hexane
  15. customto produce a white solid which
  16. filtrationwas collected by filtration
  17. customdried under vacuum

出典と根拠

ORDレコード
ord-c9db6fdd53314860afc1bc1fb4591b24
出典データセット
uspto-grants-2014_06
特許番号
US08754229B2

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