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

HRID 1194216노트

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HRID 1194216 반응식
[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

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

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온도
15 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-2f425fedb9e447b7a0e30b275f41446f
출처 데이터셋
uspto-grants-1989_03
특허 번호
US04812565

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