Lithium Hydroxide → 6-{4-[3-(2,6-Dichloro-phenyl)-5-isopropyl-isoxazol-4-ylmethoxy]-piperidin-1-yl}-1-methyl-1H-indole-3-carboxylic acid

HRID 1689788Notes

Reaction equation

HRID 1689788 reaction equation
[OH-].[Li+].C[O:4][C:5]([C:7]1[C:15]2[C:10](=[CH:11][C:12]([N:16]3[CH2:21][CH2:20][CH:19]([O:22][CH2:23][C:24]4[C:25]([C:32]5[C:37]([Cl:38])=[CH:36][CH:35]=[CH:34][C:33]=5[Cl:39])=[N:26][O:27][C:28]=4[CH:29]([CH3:31])[CH3:30])[CH2:18][CH2:17]3)=[CH:13][CH:14]=2)[N:9]([CH3:40])[CH:8]=1)=[O:6]>O1CCOCC1>[Cl:39][C:33]1[CH:34]=[CH:35][CH:36]=[C:37]([Cl:38])[C:32]=1[C:25]1[C:24]([CH2:23][O:22][CH:19]2[CH2:18][CH2:17][N:16]([C:12]3[CH:11]=[C:10]4[C:15]([C:7]([C:5]([OH:6])=[O:4])=[CH:8][N:9]4[CH3:40])=[CH:14][CH:13]=3)[CH2:21][CH2:20]2)=[C:28]([CH:29]([CH3:31])[CH3:30])[O:27][N:26]=1

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 593693356-{4-[3-(2,6-Dichloro-phenyl)-5-isopropyl-isoxazol-4-ylmethoxy]-piperidin-1-yl}-1-methyl-1H-indole-3-carboxylic acid methyl ester

Product 1

HCID 252049036-{4-[3-(2,6-Dichloro-phenyl)-5-isopropyl-isoxazol-4-ylmethoxy]-piperidin-1-yl}-1-methyl-1H-indole-3-carboxylic acidYield 86%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A solution of 2N lithium hydroxide (0.9 mL, 5 equiv, 1.8 mmole) is added to a solution of 6-{4-[3-(2,6-dichloro-phenyl)-5-isopropyl-isoxazol-4-ylmethoxy]-piperidin-1-yl}-1-methyl-1H-indole-3-carboxylic acid methyl ester (200 mg, 1.00 equiv, 0.36 mmole) in 1,4-dioxane (4 mL). The mixture is stirred at 90° C. for 24 h. The organic solvent is removed, HCl (1M) is added to adjust the pH to 3-4, and the resulting aqueous solution is extracted with dichloromethane. The organic layers are combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue is purified via flash chromatography (12 g silica) eluting with a gradient of ethyl acetate in hexane (10% to 100%) to provide the title compound as a pale brown solid (168 mg, 86%). ES/MS m/z 542.0 (M+1).

Workup

  1. customThe organic solvent is removed
  2. additionHCl (1M) is added
  3. extractionthe resulting aqueous solution is extracted with dichloromethane
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue is purified via flash chromatography (12 g silica)
  8. washeluting with a gradient of ethyl acetate in hexane (10% to 100%)

Sources & evidence

ORD record
ord-33f61b23b34247c28448dc2f5b78e32a
Source dataset
uspto-grants-2012_04
Patent number
US08153624B2

Reaction notes

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