Cyclohexyl bromide → ethyl 5-amino-1-cyclohexyl-1H-pyrazole-4-carboxylate

HRID 1804531

Reaktionsgleichung

Reaktionsgleichung von HRID 1804531
[CH2:1]([O:3][C:4]([C:6]1[C:7]([NH2:11])=[N:8][NH:9][CH:10]=1)=[O:5])[CH3:2].[CH:12]1(Br)[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1.C(=O)([O-])[O-].[K+].[K+].[OH-].[Na+]>CCCCCCCC[N+](CCCCCCCC)(CCCCCCCC)C.[Cl-].C1(C)C=CC=CC=1>[CH2:1]([O:3][C:4]([C:6]1[CH:10]=[N:9][N:8]([CH:12]2[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]2)[C:7]=1[NH2:11])=[O:5])[CH3:2]

Komponenten

7

Edukt 4

HCID 7960Cyclohexyl bromide2×HCID 11430Potassium Carbonate2×HCID 14798Sodium HydroxideHCID 178469928HCID 178469928, Verbindung

Produkt 1

HCID 351028ethyl 5-amino-1-cyclohexyl-1H-pyrazole-4-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 21218Trioctylmethylammonium chlorideKatalysatorHCID 1140TolueneLösungsmittel

Versuchsvorschrift

Ethyl-3-Aminopyrazole-4-carboxylate 9 (Acros, 15.5 g, 100.0 mmol), cyclohexylbromide (Acros, 21.9 g, 130 mmol), anhydrous potassium carbonate (Fisher, 27.6 g, 200 mmol), Adogen 464 (Acros, 2.5 g) and aqueous sodium hydroxide (0.1 mL of a 12.5M solution) were combined in 250 mL of toluene and refluxed under argon overnight. Additional cyclohexylbromide (21.9 g, 130 mmol) and potassium carbonate (27.6 g, 200 mmol) were then added and the reaction mixture was resubjected to the reaction conditions for an additional 24 hours. The reaction was permitted to cool to room temperature and the organics were washed with 100 mL water. The organic layer was separated and dried (magnesium sulfate). Concentration of the organics afforded a solid which was subjected to flash chromatography on silica gel (gradient elution 9:1 to 6:1 to 3:1 hexane:ethyl acetate) to afford two principle products. Compound 11 (923 mg, 4%) elutes first and Compound 10 (1.755 g, 7%) elutes second. A considerable amount of material was present in mixed fractions. Compound 10: MS (ES+ calculated: 237.30; found: 238.10 M+H). HPLC (98% purity, retention time 13.623 minutes—Method A); 1H NMR (400 MHz, DMSO-d6) δ 7.44 (s, 1H), 6.19 (br s, 2H), 4.43 (q, J=7 Hz, 2H), 4.05 (m, 1H), 1.83-1.22 (m, 10H), 1.23 (t, J=7 Hz, 3H). Compound 11: MS (ES+ calculated: 237.30; found: 238.14 M+H). HPLC (100% purity, retention time 13.408 minutes—Method A); 1H NMR (400 MHz, DMSO-d6) δ 7.87 (s, 1H), 5.29 (br s, 2H), 4.15 (q, J=7 Hz, 2H), 3.89 (m, 1H), 1.97-1.25 (m, 10H), 1.24 (t, J=7 Hz, 3H).

Aufarbeitung

  1. temperaturerefluxed under argon overnight
  2. customthe reaction mixture was resubjected to the reaction conditions for an additional 24 hours
  3. washthe organics were washed with 100 mL water
  4. customThe organic layer was separated
  5. dry with materialdried (magnesium sulfate)
  6. customConcentration of the organics afforded a solid which
  7. customto afford two principle products

Quellen und Nachweise

ORD-Eintrag
ord-4e1e57ea97c8494f85c1ebc606917a50
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08354414B2

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