Nitrogen → 5-(tert-Butyl)-2-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)benzaldehyde

HRID 68462

반응식

HRID 68462 반응식
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[O:12][CH2:13][C:14]([CH3:17])([CH3:16])[N:15]=2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].N#N.C1C[O:23][CH2:22]C1.C([Li])CCC>CCCCCC.CN(C=O)C>[C:1]([C:5]1[CH:6]=[CH:7][C:8]([C:11]2[O:12][CH2:13][C:14]([CH3:17])([CH3:16])[N:15]=2)=[C:9]([CH:10]=1)[CH:22]=[O:23])([CH3:4])([CH3:2])[CH3:3]

참가 물질

7

반응물 4

HCID 947NitrogenHCID 8028TetrahydrofuranHCID 3200722-(4-(Tert-butyl)phenyl)-4,4-dimethyl-4,5-dihydrooxazoleHCID 178418339Butyllithium

생성물 1

HCID 580161935-(tert-Butyl)-2-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)benzaldehyde

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8058Hexane용매

실험 절차

An oven dried 250 mL 3-neck round bottom flask was fitted with a thermometer, stir bar, septum, and nitrogen inlet. Added 8.02 g (34.7 mmol) of 2-(4-tert-butyl-phenyl)-4,4-dimethyl-4,5-dihydro-oxazole. Established and maintained N2 atmosphere. Added 100 mL of anhydrous THF. Cooled the clear solution to −78°. Stirred rapidly and added 17 mL (43 mmol) of a 2.5 M solution of n-butyllithium in hexane dropwise over 10 minutes. Stirred the clear amber solution at −20° for 4 hr. The reaction mixture became red-amber and cloudy. Cooled the mixture to −78°. Stirred rapidly and added 12 mL of DMF dropwise at a rate to keep the temperature below −60°. Stirred at −78° for 15 min. Stirred at −20° for 1 hr. Stirred at room temperature for 1 hr. Quenched with 100 mL of 0.5 M aqueous KHSO4. The aqueous phase was still strongly basic. Added more 1.0 M KHSO4 until the pH was ˜2. Diluted the two phase solution with 300 mL Et2O. Separated phases and extracted the aqueous phase with 100 mL Et2O. Washed the combined organic phases with 200 mL brine and dried over K2CO3. Filtered through 120 g of silica gel and washed through with 300 mL Et2O to remove baseline impurities. Removed the solvent on rotavap to obtain 8.18 g of the title compound as a clear yellow liquid. MS (ESI) 260 (M+H)+.

후처리

  1. customAn oven dried 250 mL 3-neck round bottom flask
  2. customwas fitted with a thermometer
  3. temperatureCooled the clear solution to −78°
  4. stirringStirred rapidly
  5. stirringStirred the clear amber solution at −20° for 4 hr
  6. temperatureCooled the mixture to −78°
  7. stirringStirred rapidly
  8. customthe temperature below −60°
  9. stirringStirred at −78° for 15 min
  10. stirringStirred at −20° for 1 hr
  11. stirringStirred at room temperature for 1 hr
  12. customQuenched with 100 mL of 0.5 M aqueous KHSO4
  13. additionAdded more 1.0 M KHSO4 until the pH was ˜2
  14. additionDiluted the two phase solution with 300 mL Et2O
  15. extractionSeparated phases and extracted the aqueous phase with 100 mL Et2O
  16. washWashed the combined organic phases with 200 mL brine
  17. dry with materialdried over K2CO3
  18. filtrationFiltered through 120 g of silica gel
  19. washwashed through with 300 mL Et2O
  20. customto remove baseline impurities
  21. customRemoved the solvent on rotavap

출처 및 근거

ORD 기록
ord-72528414127e41848155e8ac4eb27e18
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08822457B2

연결된 노트

불러오는 중…