Phosphorus oxychloride → 2-Chloro-3-ethoxycarbonyl-6,7-difluoroquinoline

HRID 1756793ノート

反応式

HRID 1756793 の反応式
[CH2:1]([O:3][C:4]([C:6]1[C:7](=O)[NH:8][C:9]2[C:14]([CH:15]=1)=[CH:13][C:12]([F:16])=[C:11]([F:17])[CH:10]=2)=[O:5])[CH3:2].P(Cl)(Cl)([Cl:21])=O>O>[Cl:21][C:7]1[C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])=[CH:15][C:14]2[C:9](=[CH:10][C:11]([F:17])=[C:12]([F:16])[CH:13]=2)[N:8]=1

参加物

4

反応物 2

HCID 24813Phosphorus oxychlorideHCID 199573073-Ethoxycarbonyl-6,7-difluorocarbostyril

生成物 1

HCID 97954612-Chloro-3-ethoxycarbonyl-6,7-difluoroquinoline

試薬・触媒・溶媒 1

HCID 962Water溶媒

反応条件

温度
70 °C

実験手順

50 g of 3-ethoxycarbonyl-6,7-difluorocarbostyril are added in the course of 10 minutes with stirring at 20° C. to 200 cm3 of phosphoryl chloride. The suspension is heated to a temperature in the region of 70° C. and maintained at this temperature for 3 hours After cooling to approximately 10° C., the solution obtained is poured with stirring into a mixture of 1,000 cm3 of water and 1,000 g of crushed ice. The temperature is allowed to rise to approximately 20° C. and the mixture is extracted with twice 500 cm3 of dichloromethane. The combined organic extracts are washed with 1,000 cm3 of water, and 1,000 cm3 of water to which sodium bicarbonate has been added to pH 7, dried over sodium sulphate, filtered and concentrated to dryness under reduced pressure (20 kPa) at approximately 40° C. 45.6 g of 2-chloro-3-ethoxycarbonyl-6,7-difluoroquinoline are obtained in the form of a beige solid, melting point 108° C., which is used without further purification for the subsequent steps. 2-Chloro-3-ethoxycarbonyl-6,7-difluoroquinoline is converted to 2-chloro-6,7-difluoro-3-quinolinecarboxylic acid according to the customary methods, and can thus lead to the benzo[b][1,8]naphthyridine derivatives described in U.S. Pat. No. 4,970,213.

後処理

  1. temperaturemaintained at this temperature for 3 hours
  2. temperatureAfter cooling to approximately 10° C.
  3. customthe solution obtained
  4. additionis poured
  5. customto rise to approximately 20° C.
  6. extractionthe mixture is extracted with twice 500 cm3 of dichloromethane
  7. washThe combined organic extracts are washed with 1,000 cm3 of water, and 1,000 cm3 of water to which sodium bicarbonate
  8. additionhas been added to pH 7
  9. dry with materialdried over sodium sulphate
  10. filtrationfiltered
  11. concentrationconcentrated to dryness under reduced pressure (20 kPa) at approximately 40° C

出典と根拠

ORDレコード
ord-bab577fd45fd423982cb77975b060162
出典データセット
uspto-grants-1995_08
特許番号
US05442070

反応ノート

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