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

HRID 2060671노트

반응식

HRID 2060671 반응식
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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 31374Dimethylacetamide용매2회

실험 절차

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, 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, 1H), 6.84 (d, J=2.0 Hz, 1H), 6.81 (dd, J=5.6, 2.4 Hz, 1H), 6.67-6.65 (m, 2H), 5.13 (s, 2H), 1.91 (s, 3H); MS (ESI): m/z 253.2 [M+H]+.

후처리

  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

출처 및 근거

ORD 기록
ord-05312cd091dd4650a16aaea5b0808e3f
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08278331B2

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