Diisopropylamine → 2-[2-(Methylthio)pyrimidin-4-yl]-1-[3-(trifluoromethyl)phenyl]ethanone

HRID 394471Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 394471
C(NC(C)C)(C)C.CON(C)[C:11](=[O:22])[C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=1.[CH3:24][C:25]1[CH:30]=[CH:29][N:28]=[C:27]([S:31][CH3:32])[N:26]=1.C([Li])CCC>O1CCCC1>[CH3:32][S:31][C:27]1[N:26]=[C:25]([CH2:24][C:11]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:19])([F:20])[F:21])[CH:13]=2)=[O:22])[CH:30]=[CH:29][N:28]=1

Komponenten

6

Edukt 4

HCID 7912DiisopropylamineHCID 8212614-Methyl-2-(methylsulfanyl)pyrimidine2×HCID 14069349N-Methoxy-N-methyl-3-(trifluoromethyl)benzamide2×HCID 178418339Butyllithium

Produkt 1

HCID 107574582-[2-(Methylthio)pyrimidin-4-yl]-1-[3-(trifluoromethyl)phenyl]ethanone

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel5×

Versuchsvorschrift

Diisopropylamine (106 mL, 761 mmol) and tetrahydrofuran (THF) 750 mL) were combined in a 3-neck 2L round bottom flask under argon. Two addition funnels, one containing a solution of Compound 1 in THF (100 mL), the other containing Compound 2 in THF (100 mL) were attached to the reaction flask. The contents of the reaction flask were cooled in an IPA/dry ice bath. A solution of n-butyl lithium (2.5M in hexanes, 304 mL, 761 mmol) was added dropwise via syringe. The THF solution of Compound 1 was added dropwise over 0.5 h. This was followed by the addition of the THF solution of Compound 2. A dark solution resulted. After 10 min, ice was added and the THF was removed in vacuo. Water was added followed by sat. sodium bicarbonate and the aqueous mixture was extracted several times with ethyl acetate. The combined organic extracts were washed with brine and dried over anhydrous sodium sulfate. The solvent was removed in vacuo to give an oil. Purification by flash column chromatography (hexane:ethyl acetate 95:5 to 75:25) gave a solid which was triturated with hexane:ether 80:20 then isolated by vacuum filtration to afford Compound 3 as a solid: 60g (220 mmol, 43%)

Aufarbeitung

  1. temperatureThe contents of the reaction flask were cooled in an IPA/dry ice bath
  2. customA dark solution resulted
  3. additionice was added
  4. customthe THF was removed in vacuo
  5. additionWater was added
  6. extractionthe aqueous mixture was extracted several times with ethyl acetate
  7. washThe combined organic extracts were washed with brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. customThe solvent was removed in vacuo
  10. customto give an oil
  11. customPurification by flash column chromatography (hexane:ethyl acetate 95:5 to 75:25)
  12. customgave a solid which
  13. customwas triturated with hexane:ether 80:20
  14. customthen isolated by vacuum filtration

Quellen und Nachweise

ORD-Eintrag
ord-93452112ff6d428687e300ae7c3b5a07
Quelldatensatz
uspto-grants-2003_08
Patentnummer
US06602872B1

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