Sodium hydride → 3-(2-Bromo-4-(trifluoromethyl)phenoxy)pyridin-2-amine

HRID 335205

反応式

HRID 335205 の反応式
[NH2:1][C:2]1[C:7]([OH:8])=[CH:6][CH:5]=[CH:4][N:3]=1.[H-].[Na+].[Br:11][C:12]1[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[CH:14][C:13]=1F>CN(C=O)C>[Br:11][C:12]1[CH:17]=[C:16]([C:18]([F:19])([F:20])[F:21])[CH:15]=[CH:14][C:13]=1[O:8][C:7]1[C:2]([NH2:1])=[N:3][CH:4]=[CH:5][CH:6]=1

参加物

5

反応物 3

HCID 24758Sodium hydride2 回HCID 281142-Amino-3-HydroxypyridineHCID 1442953-Bromo-4-fluorobenzotrifluoride

生成物 1

HCID 669947023-(2-Bromo-4-(trifluoromethyl)phenoxy)pyridin-2-amine

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

A mixture of 2-aminopyridin-3-ol (1.00 g, 9.08 mmol) and DMF (20 mL) was cooled in a 0° C. bath and sodium hydride (0.240 g, 9.49 mmol) was slowly added in portions with vigorous stirring (significant gas evolution). After the addition was completed, the mixture was stirred at ambient temperature for 30 minutes to ensure all the NaH was consumed (reaction becomes very viscous). The 2-bromo-1-fluoro-4-(trifluoromethyl)benzene (1.17 mL, 8.26 mmol) was added and the mixture heated to 110° C. under nitrogen overnight. The reaction was cooled to ambient temperature and the DMF removed under reduced pressure. The resulting black sludge was quenched with 0.5 N NaOH (100 mL) and extracted with Et2O). The organic layer was washed with 1N NaOH and brine, dried over sodium sulfate, filtered and concentrated to afford a brown solid. The solids were purified on silica gel eluting with 40% EtOAc/Hexanes to afford 3-(2-bromo-4-(trifluoromethyl)phenoxy)pyridin-2-amine the title compound.

後処理

  1. additionAfter the addition
  2. stirringthe mixture was stirred at ambient temperature for 30 minutes
  3. customwas consumed
  4. custom(reaction becomes very viscous)
  5. temperaturethe mixture heated to 110° C. under nitrogen overnight
  6. temperatureThe reaction was cooled to ambient temperature
  7. customthe DMF removed under reduced pressure
  8. customThe resulting black sludge was quenched with 0.5 N NaOH (100 mL)
  9. extractionextracted with Et2O)
  10. washThe organic layer was washed with 1N NaOH and brine
  11. dry with materialdried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customto afford a brown solid
  15. customThe solids were purified on silica gel eluting with 40% EtOAc/Hexanes

出典と根拠

ORDレコード
ord-a96acb9d53b34945b80914c6ecaea32a
出典データセット
uspto-grants-2014_11
特許番号
US08883828B2

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