Diisopropylethylamine → 5-Bromo-N-((1SR,2RS)-2-hydroxy-cyclohexyl)-6-(2,2,2-trifluoro-ethoxy)-nicotinamide

HRID 1516381Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1516381
[Br:1][C:2]1[C:3]([O:11][CH2:12][C:13]([F:16])([F:15])[F:14])=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([OH:9])=O.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)C(C)C)(C)C.Cl.[NH2:49][CH:50]1[CH2:55][CH2:54][CH2:53][CH2:52][CH:51]1[OH:56]>CN(C=O)C>[Br:1][C:2]1[C:3]([O:11][CH2:12][C:13]([F:16])([F:15])[F:14])=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([NH:49][CH:50]1[CH2:55][CH2:54][CH2:53][CH2:52][CH:51]1[OH:56])=[O:9]

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 218772022-Aminocyclohexanol hydrochlorideHCID 581925925-Bromo-6-(2,2,2-trifluoroethoxy)-3-pyridinecarboxylic acid

Produkt 1

HCID 581925915-Bromo-N-((1SR,2RS)-2-hydroxy-cyclohexyl)-6-(2,2,2-trifluoro-ethoxy)-nicotinamideAusbeute 81,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

5-Bromo-6-(2,2,2-trifluoro-ethoxy)-nicotinic acid (75.0 g, 0.25 mol) was dissolved in DMF (850 mL). To the solution was added TBTU (91.0 g, 0.275 mol), N,N-diisopropylethyl amine (214 mL, 1.25 mol) and (1SR,2RS)-2-amino-cyclohexanol hydrochloride (41.7 g, 0.275 mol). The reaction mixture was stirred for 1.5 h at room temperature. The solvent was evaporated in vacuo, the residue was partitioned between ethyl acetate (2500 mL) and 1 N sodium hydroxide solution (2000 mL), the water phase was separated, extracted once more with ethyl acetate (1000 mL) and the organic phases were washed 2 times with water (2×1500 mL). Organic phases were pooled, dried with MgSO4 and concentrated to about 900 mL. The product precipitated upon stirring and cooling to 0° C. Filtration, washing with ethyl acetate/n-heptane (1:1) and drying in vacuo gave the title compound (81.1 g) as a white solid; MS (ISP) 397, 399 (M)+.

Aufarbeitung

  1. customThe solvent was evaporated in vacuo
  2. customthe residue was partitioned between ethyl acetate (2500 mL) and 1 N sodium hydroxide solution (2000 mL)
  3. customthe water phase was separated
  4. extractionextracted once more with ethyl acetate (1000 mL)
  5. washthe organic phases were washed 2 times with water (2×1500 mL)
  6. dry with materialdried with MgSO4
  7. concentrationconcentrated to about 900 mL
  8. customThe product precipitated
  9. stirringupon stirring
  10. temperaturecooling to 0° C
  11. filtrationFiltration
  12. washwashing with ethyl acetate/n-heptane (1:1)
  13. customdrying in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-74a4fb52365c421cb426c6bba343c669
Quelldatensatz
uspto-grants-2012_07
Patentnummer
US08227491B2

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