Potassium Hydroxide → 6-(4-((5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl)methoxy)piperidin-1-yl)-1-methyl-1H-indole-3-carboxylic acid

HRID 1689813Notes

Reaction equation

HRID 1689813 reaction equation
C[O:2][C:3]([C:5]1[C:13]2[C:8](=[CH:9][C:10]([N:14]3[CH2:19][CH2:18][CH:17]([O:20][CH2:21][C:22]4[C:23]([C:30]5[C:35]([Cl:36])=[CH:34][CH:33]=[CH:32][C:31]=5[Cl:37])=[N:24][O:25][C:26]=4[CH:27]4[CH2:29][CH2:28]4)[CH2:16][CH2:15]3)=[CH:11][CH:12]=2)[N:7]([CH3:38])[CH:6]=1)=[O:4].[OH-].[K+]>CO.C1COCC1.O1CCOCC1>[CH:27]1([C:26]2[O:25][N:24]=[C:23]([C:30]3[C:31]([Cl:37])=[CH:32][CH:33]=[CH:34][C:35]=3[Cl:36])[C:22]=2[CH2:21][O:20][CH:17]2[CH2:18][CH2:19][N:14]([C:10]3[CH:9]=[C:8]4[C:13]([C:5]([C:3]([OH:4])=[O:2])=[CH:6][N:7]4[CH3:38])=[CH:12][CH:11]=3)[CH2:15][CH2:16]2)[CH2:28][CH2:29]1

Participants

6

Reactant 2

HCID 14797Potassium HydroxideHCID 593693306-{4-[5-Cyclopropyl-3-(2,6-dichloro-phenyl)-isoxazol-4-ylmethoxy]-piperidin-1-yl}-1-methyl-1H-indole-3-carboxylic acid methyl ester

Product 1

HCID 252047676-(4-((5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl)methoxy)piperidin-1-yl)-1-methyl-1H-indole-3-carboxylic acid

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

In a 500 mL round bottom flask under nitrogen, containing a solution of 9 g (16.23 mmol) of 6-{4-[5-cyclopropyl-3-(2,6-dichloro-phenyl)-isoxazol-4-ylmethoxy]-piperidin-1-yl}-1-methyl-1H-indole-3-carboxylic acid methyl ester in 80 mL of methanol, 80 mL of THF and 30 mL dioxane, is added 2N KOH (40 mL, 81.16 mmol). The reaction mixture is stirred at 70° C. overnight. The reaction mixture is then cooled to room temperature, and the solvent removed under vacuum. The residue is diluted with 100 mL of water, and washed with MTBE. The aqueous layer is acidified (pH 5) by addition of 2N HCl, then, it is extracted with CH2Cl2 (3×150 mL). The organics are dried over MgSO4, filtered, and evaporated to yield a light green solid that is recrystallized from MeOH/CH3CN (6.05 g (70%)). MS (m/e): 540 (M+1).

Workup

  1. temperatureThe reaction mixture is then cooled to room temperature
  2. customthe solvent removed under vacuum
  3. additionThe residue is diluted with 100 mL of water
  4. washwashed with MTBE
  5. additionby addition of 2N HCl
  6. extractionit is extracted with CH2Cl2 (3×150 mL)
  7. dry with materialThe organics are dried over MgSO4
  8. filtrationfiltered
  9. customevaporated
  10. customto yield a light green solid that
  11. customis recrystallized from MeOH/CH3CN (6.05 g (70%))

Sources & evidence

ORD record
ord-2eae1537a4bd48c699d3ffbe01af1ec8
Source dataset
uspto-grants-2012_04
Patent number
US08153624B2

Reaction notes

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