Trimethyl phosphite → 7-Bromo-6-methoxyisoquinoline

HRID 228877노트

반응식

HRID 228877 반응식
[Br:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH:5]=O.CO[CH:14](OC)[CH2:15][NH2:16].ClC(OCC)=O.P(OC)(OC)OC.[OH-].[Na+]>C1C=CC=CC=1.[Ti](Cl)(Cl)(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]2[C:7]([CH:14]=[CH:15][N:16]=[CH:5]2)=[CH:8][C:9]=1[O:10][CH3:11]

참가 물질

8

반응물 5

HCID 8472Trimethyl phosphiteHCID 10928Ethyl chloroformateHCID 14798Sodium HydroxideHCID 89728Aminoacetaldehyde dimethyl acetalHCID 986623-Bromo-4-methoxybenzaldehyde

생성물 1

HCID 230784917-Bromo-6-methoxyisoquinoline수율 26.2%

시약·촉매·용매 2

HCID 24193Titanium Tetrachloride촉매HCID 241Benzene용매

반응 조건

온도
-10 °C

실험 절차

3-Bromo-4-methoxybenzaldehyde (10.0 g) was dissolved in benzene (100 ml) to prepare a solution. 2,2-Dimethoxy-ethylamine (4.89 g) was added to the solution, and the mixture was heated under reflux overnight. The solvent was removed by distillation under the reduced pressure, and the residue was then dissolved in tetrahydrofuran (100 ml) to prepare a solution which was then cooled to −10° C. Ethyl chloroformate (5.05 g) and trimethyl phosphite (6.92 g) were added thereto, and the mixture was stirred at room temperature overnight. The solvent was removed by distillation under the reduced pressure, the residue was then dissolved in dichloromethane (100 ml) to prepare a solution. Titanium tetrachloride (53.0 g) was added to the solution, and the mixture was heated under reflux for 36 hr. The reaction solution was cooled to room temperature, was then neutralized with a 1 N aqueous sodium hydroxide solution, and was extracted with 3 N hydrochloric acid. The aqueous layer was made basic with a 3 N aqueous sodium hydroxide solution, was then extracted with dichloromethane, and the solvent was removed by distillation under the reduced pressure to give 7-bromo-6-methoxyisoquinoline (2.90 g, yield 26%).

후처리

  1. customto prepare a solution
  2. temperaturethe mixture was heated
  3. temperatureunder reflux overnight
  4. customThe solvent was removed by distillation under the reduced pressure
  5. dissolutionthe residue was then dissolved in tetrahydrofuran (100 ml)
  6. customto prepare a solution which
  7. customThe solvent was removed by distillation under the reduced pressure
  8. dissolutionthe residue was then dissolved in dichloromethane (100 ml)
  9. customto prepare a solution
  10. temperaturethe mixture was heated
  11. temperatureunder reflux for 36 hr
  12. temperatureThe reaction solution was cooled to room temperature
  13. extractionwas extracted with 3 N hydrochloric acid
  14. extractionwas then extracted with dichloromethane
  15. customthe solvent was removed by distillation under the reduced pressure

출처 및 근거

ORD 기록
ord-de25ba9881644dd79fa32f2df0fad604
출처 데이터셋
uspto-grants-2009_07
특허 번호
US07560558B2

반응 노트

불러오는 중…