Hydrochloric Acid → 2-(2-Isopropoxy-3-methylphenyl)-1-(4-pyridinyl)ethanone

HRID 2074413

반응식

HRID 2074413 반응식
C1(OP([CH:17](NC2C=CC=CC=2)[C:18]2[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=2)(=O)OC2C=CC=CC=2)C=CC=CC=1.[CH3:31][C:32]1[C:33]([O:40][CH:41]([CH3:43])[CH3:42])=[C:34]([CH:37]=[CH:38][CH:39]=1)[CH:35]=O.C([O-])([O-])=[O:45].[Cs+].[Cs+].Cl.[OH-].[Na+]>C1COCC1.CC(O)C>[CH:41]([O:40][C:33]1[C:34]([CH3:35])=[CH:37][CH:38]=[CH:39][C:32]=1[CH2:31][C:17]([C:18]1[CH:19]=[CH:20][N:21]=[CH:22][CH:23]=1)=[O:45])([CH3:43])[CH3:42]

참가 물질

8

반응물 5

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 14798Sodium HydroxideHCID 423769Diphenyl (phenylamino)(pyridin-4-yl)methylphosphonateHCID 498745213-Methyl-2-[(propan-2-yl)oxy]benzaldehyde

생성물 1

HCID 588701372-(2-Isopropoxy-3-methylphenyl)-1-(4-pyridinyl)ethanone수율 24.1%

시약·촉매·용매 2

HCID 3776Isopropanol용매HCID 8028Tetrahydrofuran용매

실험 절차

Combine [(phenylamino)-4-pyridinylmethyl]phosphonic acid diphenyl ester (29.4 g, 0.071 mol), 3-methyl-2-isopropoxybenzaldehyde (13.0 g, 0.073 mol) and Cs2CO3 (29.9 g, 0.092 mol) in THF (225 mL) and IPA (75 mL). Stir the mixture under nitrogen for 48 hr before adding to 3M aqueous HCl under nitrogen. Allowed the red solution to stand for 3 hr during which time the red color fades to yellow. Cool the solution was to 10° before neutralizing to pH 12 by the slow addition of 50% aqueous NaOH. Extract the mixture with EtOAc and then wash the organic layer with H2O. Dry over MgSO4, and evaporate the solvent to give a residue. Purify the residue by chromatography over SiO2 using EtOAc:heptane (1:1). Receive fractions containing pure product and some fractions containing a mixture of product and the aniline Schiff's base of the product. Dissolve the latter mixture in 3M aqueous HCl and allow to stand for 6 hr, at which time the red color discharges. Neutralize the acid solution with NaHCO3 and extract with EtOAc, wash the extract with H2O and dry over MgSO4. Evaporate the solvent to obtain 4.6 g of 2-(2-isopropoxy-3-methylphenyl)-1-(4-pyridinyl)ethanone which when blended with the pure product from the column gives a total yield of 16.9 g (89%); 1H-NMR (CDCl3) δ 8.8-6.9 (m, 7H), 4.3 (s, 2H), 4.2 (m, 1H), 2.3 (s, 3H), 1.3 (d, 6H).

후처리

  1. waitAllowed the red solution to stand for 3 hr during which time
  2. temperatureCool the solution
  3. customwas to 10°
  4. extractionExtract the mixture with EtOAc
  5. washwash the organic layer with H2O
  6. dry with materialDry over MgSO4
  7. customevaporate the solvent
  8. customto give a residue
  9. customPurify the residue by chromatography over SiO2
  10. additioncontaining pure product
  11. additionsome fractions containing
  12. additiona mixture of product
  13. dissolutionDissolve the latter mixture in 3M aqueous HCl
  14. waitto stand for 6 hr, at which time
  15. extractionNeutralize the acid solution with NaHCO3 and extract with EtOAc
  16. washwash the
  17. extractionextract with H2O
  18. dry with materialdry over MgSO4
  19. customEvaporate the solvent

출처 및 근거

ORD 기록
ord-508980dc52d84ea5badcb6ce4c8ac796
출처 데이터셋
uspto-grants-2011_04
특허 번호
US07919508B2

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