Tetrahydrofuran → (R)-methyl-2-fluoro-4-(3-isopropyl-2-oxo-4-(4-(trifluoromethyl)pyrimidin-2-yl)piperazin-1-yl)-5-nitrobenzoate

HRID 1051817Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1051817
[CH:1]([C@H:4]1[N:9]([C:10]2[N:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[CH:12][N:11]=2)[CH2:8][CH2:7][NH:6][C:5]1=[O:20])([CH3:3])[CH3:2].CC([O-])(C)C.[K+].C1COCC1.[F:32][C:33]1[CH:42]=[C:41](F)[C:40]([N+:44]([O-:46])=[O:45])=[CH:39][C:34]=1[C:35]([O:37][CH3:38])=[O:36].[NH4+].[Cl-]>CN(C=O)C.CCOC(C)=O>[CH3:38][O:37][C:35](=[O:36])[C:34]1[CH:39]=[C:40]([N+:44]([O-:46])=[O:45])[C:41]([N:6]2[CH2:7][CH2:8][N:9]([C:10]3[N:15]=[C:14]([C:16]([F:17])([F:19])[F:18])[CH:13]=[CH:12][N:11]=3)[C@H:4]([CH:1]([CH3:3])[CH3:2])[C:5]2=[O:20])=[CH:42][C:33]=1[F:32]

Komponenten

8

Edukt 5

HCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 11447263Methyl 2,4-difluoro-5-nitrobenzoateHCID 23665647Potassium tert-butoxideHCID 89814804(R)-3-isopropyl-4-(4-(trifluoromethyl)pyrimidin-2-yl)piperazin-2-one

Produkt 1

HCID 89815945(R)-methyl-2-fluoro-4-(3-isopropyl-2-oxo-4-(4-(trifluoromethyl)pyrimidin-2-yl)piperazin-1-yl)-5-nitrobenzoate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a solution of (R)-3-isopropyl-4-(4-(trifluoromethyl)pyrimidin-2-yl)piperazin-2-one (986 mg, 3.42 mmol) in DMF (5 mL) was added a 2 M solution of KOtBu in THF (2.14 mL, 4.28 mmol) dropwise at 0° C. The reaction stirred for 1 h at 0° C. and was then cooled to −78° C. In a separate flask, a solution of methyl 2,4-difluoro-5-nitrobenzoate (928 mg, 4.28 mmol) in DMF (15 mL) was cooled to −78° C. To this solution was added a solution of the above anion via cannula at −78° C. over a 5 min period. The reaction was allowed to warm to −50° C. and stirred at this temperature for 2 h. Sat. aq. NH4Cl (20 mL) was added to quench the reaction, followed by EtOAc (30 mL). The EtOAc layer was separated and the aqueous layer was extracted with EtOAc (3×15 mL). The EtOAc layers were combined, dried and evaporated to give crude (R)-methyl-2-fluoro-4-(3-isopropyl-2-oxo-4-(4-(trifluoromethyl)pyrimidin-2-yl)piperazin-1-yl)-5-nitrobenzoate which was taken on directly for the next step without further purification.

Aufarbeitung

  1. temperaturewas then cooled to −78° C
  2. additionTo this solution was added a solution of the above anion via cannula at −78° C. over a 5 min period
  3. temperatureto warm to −50° C.
  4. stirringstirred at this temperature for 2 h
  5. customto quench
  6. customthe reaction
  7. customThe EtOAc layer was separated
  8. extractionthe aqueous layer was extracted with EtOAc (3×15 mL)
  9. customdried
  10. customevaporated

Quellen und Nachweise

ORD-Eintrag
ord-3e11e6e5c5f14cb59ec5b83ca7bd650d
Quelldatensatz
uspto-grants-2016_07
Patentnummer
US09388190B2

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