Water → 7-Chloro-2-(2-chloroethyl)-2,3-dihydro-4,8-dimethylpyrido[3,2-f]-1,4-oxazepin-5(4H)-one

HRID 247300ノート

反応式

HRID 247300 の反応式
[H-].[Na+].Cl[C:4]1[C:9]([C:10]([OH:12])=O)=[CH:8][C:7]([Cl:13])=[C:6]([CH3:14])[N:5]=1.[C:15]([Cl:20])(=O)[C:16](Cl)=O.[OH2:21]>O1CCCC1>[Cl:13][C:7]1[C:6]([CH3:14])=[N:5][C:4]2[O:21][CH:9]([CH2:16][CH2:15][Cl:20])[CH2:4][N:5]([CH3:6])[C:10](=[O:12])[C:9]=2[CH:8]=1

参加物

6

反応物 4

HCID 962WaterHCID 24758Sodium hydrideHCID 65578Oxalyl chlorideHCID 140985062,5-Dichloro-6-methyl-3-pyridinecarboxylic acid

生成物 1

HCID 143915077-Chloro-2-(2-chloroethyl)-2,3-dihydro-4,8-dimethylpyrido[3,2-f]-1,4-oxazepin-5(4H)-one収率 30%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
15 °C

実験手順

To a suspension of 29.6 g of 60% sodium hydride (0.74 mole) in 300 ml of tetrahydrofuran under a nitrogen blanket and at reflux was added dropwise at a rate to maintain good reflux a solution of 74.5 g (0.36 mole) of 2,5-dichloro-6-methyl-3-pyridinecarboxylic acid and 36.5 g (0.36 mole) of N-methylpyrrolidinol in 300 ml of tetrahydrofuran. The mixture was heated at reflux for 2 hr and cooled to 15° C. To the mixture was added dropwise, carefully, 47.2 g of oxalyl chloride between 15°-20° C. The mixture was stirred at room temperature for 1.5 hr followed by addition of 400 ml of water. Stirring was continued for 10 minutes. Tetrahydrofuran was removed by rotary evaporation and the remaining aqueous extracted with 3×200 ml of toluene. The combined organic layers were washed with 300 ml of water, dried over sodium sulfate, filtered, charcoaled, and concentrated by rotary evaporation. The residue was crystallized from isopropyl alcohol/isopropyl ether to give 33 g (30%) of crystals. A 3 g sample was recrystallized from isopropyl ether to give an analytically pure sample, m.p. 65°-69° C.

後処理

  1. temperatureat reflux
  2. additionwas added dropwise at a rate
  3. temperatureto maintain good
  4. temperatureThe mixture was heated
  5. temperatureat reflux for 2 hr
  6. additionTo the mixture was added dropwise
  7. custombetween 15°-20° C
  8. stirringStirring
  9. waitwas continued for 10 minutes
  10. customTetrahydrofuran was removed by rotary evaporation
  11. extractionthe remaining aqueous extracted with 3×200 ml of toluene
  12. washThe combined organic layers were washed with 300 ml of water
  13. dry with materialdried over sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated by rotary evaporation
  16. customThe residue was crystallized from isopropyl alcohol/isopropyl ether

出典と根拠

ORDレコード
ord-616c6762e2114b078554f98fd14acba1
出典データセット
uspto-grants-1987_11
特許番号
US04705853

反応ノート

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