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 1689812Notes

Reaction equation

HRID 1689812 reaction equation
[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]

Participants

7

Reactant 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

Product 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 esterYield 43.3%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
120 °C

Procedure

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)

Workup

  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

Sources & evidence

ORD record
ord-fb9469ac23fd43e7a4daf1156e4835f8
Source dataset
uspto-grants-2012_04
Patent number
US08153624B2

Reaction notes

Loading…