Citric Acid → 6-{2-[2-(4-Chloro-phenyl)-2,4,5,6-tetrahydro-cyclopentapyrazol-3-yl]-2-cyclohexyl-ethoxy}-nicotinic acid methyl ester

HRID 889381Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 889381
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH:13]([CH:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)[C:14](NC3CCCCC3)=[O:15])=[C:11]3[CH2:29][CH2:30][CH2:31][C:10]3=[N:9]2)=[CH:4][CH:3]=1.[C:32]([O-])([O-])=[O:33].[K+].[K+].ClC1C=CC([N:45]2[C:49]([CH:50]([CH:57]3[CH2:62][CH2:61]CCC3)[CH2:51][O:52]S(C)(=O)=O)=C3CCCC3=N2)=CC=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C.CCOC(C)=O>[CH3:32][O:33][C:51](=[O:52])[C:50]1[CH:57]=[CH:62][C:61]([O:15][CH2:14][CH:13]([C:12]2[N:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)[N:9]=[C:10]3[CH2:31][CH2:30][CH2:29][C:11]=23)[CH:23]2[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)=[N:45][CH:49]=1

Komponenten

7

Edukt 4

HCID 311Citric AcidHCID 11430Potassium CarbonateHCID 533902542-[2-(4-Chloro-phenyl)-2,4,5,6-tetrahydro-cyclopentapyrazol-3-yl]-2,N-dicyclohexyl-acetamideHCID 86657984Methanesulfonic acid 2-[2-(4-chloro-phenyl)-2,4,5,6-tetrahydro-cyclopentapyrazol-3-yl]-2-cyclohexyl-ethyl ester

Produkt 1

HCID 673871806-{2-[2-(4-Chloro-phenyl)-2,4,5,6-tetrahydro-cyclopentapyrazol-3-yl]-2-cyclohexyl-ethoxy}-nicotinic acid methyl esterAusbeute 67 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a solution of methyl 6-hydroxynicotinate 4 (80 mg, 0.19 mmol; CAS Reg. No. 10128-91-3) in dry DMF (3 ml) was added dry K2CO3 (29 mg, 0.226 mmol) at 0° C. The reaction mixture was stirred for 15 minutes at 0° C. Methanesulfonic acid 2-[2-(4-chloro-phenyl)-2,4,5,6-tetrahydro-cyclopentapyrazol-3-yl]-2-cyclohexyl-ethyl ester (35 mg, 0.227 mmol) dissolved in dry DMF (1 ml) was added at 0° C. The reaction mixture was heated to 100° C. in a sealed tube for 12 h. 10% Aqueous citric acid solution (10 ml) and EtOAc (5 ml) were added to the reaction mixture. The layers were separated and the aqueous layer was extracted one more time with EtOAc (5 ml). The combined organic layers were washed with brine (5 ml) and dried over Na2SO4. The solvent was removed under reduced pressure to give a residue which was purified by column chromatography over silica gel (20% EtOAc/hexane) to give the title compound (60.2 mg, 0.12 mmol; 67%) as off-white solid.

Aufarbeitung

  1. additionwas added at 0° C
  2. temperatureThe reaction mixture was heated to 100° C. in a sealed tube for 12 h
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted one more time with EtOAc (5 ml)
  5. washThe combined organic layers were washed with brine (5 ml)
  6. dry with materialdried over Na2SO4
  7. customThe solvent was removed under reduced pressure
  8. customto give a residue which
  9. customwas purified by column chromatography over silica gel (20% EtOAc/hexane)

Quellen und Nachweise

ORD-Eintrag
ord-c16aff626632482693e797bb76495245
Quelldatensatz
uspto-grants-2012_08
Patentnummer
US08252826B2

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