2,4-Dichloropyridine → 4-(2-Chloro-pyridin-4-yloxy)-2-fluoro-3-methyl-phenylamine

HRID 1098551ノート

反応式

HRID 1098551 の反応式
CC(C)([O-])C.[K+].[NH2:7][C:8]1[CH:13]=[CH:12][C:11]([OH:14])=[C:10]([CH3:15])[C:9]=1[F:16].[Cl:17][C:18]1[CH:23]=[C:22](Cl)[CH:21]=[CH:20][N:19]=1>CC(N(C)C)=O>[Cl:17][C:18]1[CH:23]=[C:22]([O:14][C:11]2[CH:12]=[CH:13][C:8]([NH2:7])=[C:9]([F:16])[C:10]=2[CH3:15])[CH:21]=[CH:20][N:19]=1

参加物

5

反応物 3

HCID 335152,4-DichloropyridineHCID 23665647Potassium tert-butoxideHCID 552890104-Amino-3-fluoro-2-methylphenol

生成物 1

HCID 866196704-(2-Chloro-pyridin-4-yloxy)-2-fluoro-3-methyl-phenylamine収率 42.2%

試薬・触媒・溶媒 1

HCID 31374Dimethylacetamide溶媒2 回

実験手順

Potassium tert-butoxide (3.5 g, 31 mmol) was added to a solution of 4-amino-3-fluoro-2-methyl-phenol (4.2 g, 30 mmol) in dimethylacetamide. The mixture was stirred at RT for 30 min. A solution of 2,4-dichloropyridine (4.38 g, 30 mmol) in dimethylacetamide was added and the mixture was heated at 100° C. overnight. The reaction mixture was concentrated in vacuo and the residue was dissolved in ethyl acetate (200 mL) and filtered through silica gel. The filter cake was washed with ethyl acetate and the combined filtrates were concentrated in vacuo and purified by silica gel chromatography to give 4-(2-chloro-pyridin-4-yloxy)-2-fluoro-3-methyl-phenylamine (3.2 g, 42% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.21 (d, J=6.4 Hz, 1 H), 6.84 (d, J=2.0 Hz, 1 H), 6.81 (dd, J=5.6, 2.4 Hz, 1 H), 6.67-6.65 (m, 2 H), 5.13 (s, 2H), 1.91 (s, 3 H); MS (ESI): m/z 253.2 [M+H]+.

後処理

  1. temperaturethe mixture was heated at 100° C. overnight
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. dissolutionthe residue was dissolved in ethyl acetate (200 mL)
  4. filtrationfiltered through silica gel
  5. washThe filter cake was washed with ethyl acetate
  6. concentrationthe combined filtrates were concentrated in vacuo
  7. custompurified by silica gel chromatography

出典と根拠

ORDレコード
ord-e97e57f5616f4be59493124dfaf0d195
出典データセット
uspto-grants-2012_03
特許番号
US08143293B2

反応ノート

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