Potassium Carbonate → 6-{4-[5-Cyclopropyl-3-(2,6-dichloro-phenyl)-isoxazol-4-ylmethoxy]-piperidin-1-yl}-1-methyl-1H-indole-3-carboxylic acid methyl ester

HRID 1689812Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1689812
[CH:1]1([C:4]2[O:8][N:7]=[C:6]([C:9]3[C:14]([Cl:15])=[CH:13][CH:12]=[CH:11][C:10]=3[Cl:16])[C:5]=2[CH2:17][O:18][CH:19]2[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]2)[CH2:3][CH2:2]1.[CH3:25][O:26][C:27]([C:29]1[C:37]2[C:32](=[CH:33][C:34](Br)=[CH:35][CH:36]=2)[N:31]([CH3:39])[CH:30]=1)=[O:28].C(=O)([O-])[O-].[K+].[K+].N1CCC[C@H]1C(O)=O>CS(C)=O.[Cu]I>[CH3:25][O:26][C:27]([C:29]1[C:37]2[C:32](=[CH:33][C:34]([N:22]3[CH2:23][CH2:24][CH:19]([O:18][CH2:17][C:5]4[C:6]([C:9]5[C:10]([Cl:16])=[CH:11][CH:12]=[CH:13][C:14]=5[Cl:15])=[N:7][O:8][C:4]=4[CH:1]4[CH2:2][CH2:3]4)[CH2:20][CH2:21]3)=[CH:35][CH:36]=2)[N:31]([CH3:39])[CH:30]=1)=[O:28]

Komponenten

7

Edukt 4

HCID 11430Potassium CarbonateHCID 145742L-ProlineHCID 57443279Methyl 6-bromo-1-methyl-1H-indole-3-carboxylateHCID 593693344-{[5-Cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}piperidine

Produkt 1

HCID 593693306-{4-[5-Cyclopropyl-3-(2,6-dichloro-phenyl)-isoxazol-4-ylmethoxy]-piperidin-1-yl}-1-methyl-1H-indole-3-carboxylic acid methyl esterAusbeute 43,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 679Dimethyl SulfoxideLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

A 250 mL sealed round bottom flask under nitrogen is charged with 4-[5-cyclopropyl-3-(2,6-dichloro-phenyl)-isoxazol-4-ylmethoxy]-piperidine (15 g, 40.84 mmol), 6-bromo-1-methyl-1H-indole-3-carboxylic acid methyl ester (15.33 g, 57.18 mmol); potassium carbonate (11.29 g, 81.68 mmol), copper(I) iodide (3.11 g, 16.34 mmol), and proline (1.88 g, 16.34 mmol) in 80 mL of dimethyl sulfoxide. The reaction mixture is heated at 120° C. for 16 h. Then, it is cooled down to room temperature, quenched with water (200 mL) and extracted with EtOAc (3×150 mL). The organics are washed with water and brine, dried over MgSO4, filtered and evaporated. The crude is purified by flash silica gel chromatography using hex/EtOAc 8:2 to 1:1 as eluent system, to obtain 9.8 g of the title compound as a white solid (43%). MS (m/e): 554 (M+1)

Aufarbeitung

  1. customA 250 mL sealed round bottom flask under nitrogen
  2. temperatureThen, it is cooled down to room temperature
  3. customquenched with water (200 mL)
  4. extractionextracted with EtOAc (3×150 mL)
  5. washThe organics are washed with water and brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customThe crude is purified by flash silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-fb9469ac23fd43e7a4daf1156e4835f8
Quelldatensatz
uspto-grants-2012_04
Patentnummer
US08153624B2

Notizen zur Reaktion

Wird geladen…