Methanol → 2-Acetyl-5-amino-3-trifluoromethylpyridine

HRID 576166ノート

反応式

HRID 576166 の反応式
Cl[C:2]1[N:7]=[CH:6][C:5]([NH2:8])=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10].[C:13]([O-:16])(O)=O.[Na+].[CH3:18]O>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:8][C:5]1[CH:4]=[C:3]([C:9]([F:12])([F:11])[F:10])[C:2]([C:13](=[O:16])[CH3:18])=[N:7][CH:6]=1

参加物

5

反応物 3

HCID 887MethanolHCID 516892Sodium BicarbonateHCID 135322446-Chloro-5-(trifluoromethyl)pyridin-3-amine2 回

生成物 1

HCID 586455412-Acetyl-5-amino-3-trifluoromethylpyridine収率 49.1%

試薬・触媒・溶媒 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒

反応条件

温度
110 °C

実験手順

To a mixture of 6-chloro-5-(trifluoromethyl)pyridin-3-amine (200 mg, 1.018 mmol) in MeOH (3 mL) was added 6-chloro-5-(trifluoromethyl)pyridin-3-amine (200 mg, 1.018 mmol), NaHCO3 (171 mg, 2.035 mmol) and PdCl2(dppf) (74.5 mg, 0.102 mmol). The mixture was stirred under a N2 atmosphere at 110° C. for 30 min under microwave. Then the reaction residue was filtered and the solid was washed by MeOH. Then 6M HCl was added to the solution, which was stirred a rt for 1 h and then concentrated to give the crude product. The crude product was purified by preparative TLC (PE/EA=1:1, Rf=0.6) to yield a light yellow solid of 1-(5-amino-3-(trifluoromethyl)pyridin-2-yl)ethanone (120 mg, 0.500 mmol, 49.1% yield): 1H NMR (400 MHz, CD3OD) δ 8.10 (d, J=2.43 Hz, 1H), 7.30 (d, J=2.43 Hz, 1H), 2.56 (s, 3H); ES-LCMS m/z 205.0 (M+H).

後処理

  1. filtrationThen the reaction residue was filtered
  2. washthe solid was washed by MeOH
  3. additionThen 6M HCl was added to the solution, which
  4. stirringwas stirred a rt for 1 h
  5. concentrationconcentrated
  6. customto give the crude product
  7. customThe crude product was purified by preparative TLC (PE/EA=1:1, Rf=0.6)

出典と根拠

ORDレコード
ord-817386399b054733aca7d86915899d33
出典データセット
uspto-grants-2015_05
特許番号
US09035063B2

反応ノート

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