Sodium Hydroxide → 6-Chloro-5-[4-(1-hydroxy-2-methylpropan-2-yl)-3-methoxyphenyl]-1H-indole-3-carboxylic acid

HRID 1054725Notes

Reaction equation

HRID 1054725 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([O:13]C)=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:15]1[CH:20]=[CH:19][C:18]([C:21]([CH3:25])([CH3:24])[CH2:22][OH:23])=[C:17]([O:26][CH3:27])[CH:16]=1.[OH-].[Na+]>CO>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([OH:13])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:15]1[CH:20]=[CH:19][C:18]([C:21]([CH3:25])([CH3:24])[CH2:22][OH:23])=[C:17]([O:26][CH3:27])[CH:16]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 86698724Methyl 6-chloro-5-(4-(1-hydroxy-2-methylpropan-2-yl)-3-methoxyphenyl)-1H-indole-3-carboxylate

Product 1

HCID 717659536-Chloro-5-[4-(1-hydroxy-2-methylpropan-2-yl)-3-methoxyphenyl]-1H-indole-3-carboxylic acidYield 75.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of the methyl 6-chloro-5-(4-(1-hydroxy-2-methylpropan-2-yl)-3-methoxyphenyl)-1H-indole-3-carboxylate (25 mg, 0.064 mmol), 2.4 ml of methanol (2.4 mL), and 0.8 mL of 1 M aqueous solution of sodium hydroxide (0.8 mL, 0.8 mmol) was stirred at 70° C. for 24 hours—the starting material is consumed by TLC and LCMS. The reaction mixture was cooled to room temperature, diluted with 1 M solution of potassium bisulfate (1 mL) and the obtained mixture was concentrated. The residue was partitioned between ethyl acetate and water. The organic extract was washed with brine, dried over anhydrous magnesium sulfate and loaded on silica gel. A silica gel column was equilibrated with 30% ethyl acetate in heptane. Chromatography on this column, eluting with a solution of 3% of acetic acid and 30% of ethyl acetate in heptane gave the title compound (18 mg, 73% yield). MS (ES−) 372.1 (M−H)−. Retention time: 3.00 min Column: Phenomenex Gemini-NX, 4.6 mm×50 mm, C18, 3 μm, 110A; Column Temperature 60° C. Mobile Phase A: 0.1% formic acid in water (v/v); Mobile Phase B: 0.1% formic acid in acetonitrile (v/v) Gradient Profile: Flow-1.5 mL/min. Initial conditions: A-95%, B-5%; Linear Ramp to A-0%, B-100% over 0.0-4.10 min; hold at A-0%, B-100% from 4.10-4.50 min; return to initial conditions 4.60-5.0 min.

Workup

  1. customis consumed by TLC and LCMS
  2. temperatureThe reaction mixture was cooled to room temperature
  3. additiondiluted with 1 M solution of potassium bisulfate (1 mL)
  4. concentrationthe obtained mixture was concentrated
  5. customThe residue was partitioned between ethyl acetate and water
  6. extractionThe organic extract
  7. washwas washed with brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. washChromatography on this column, eluting with a solution of 3% of acetic acid and 30% of ethyl acetate in heptane

Sources & evidence

ORD record
ord-e021135d9948436799beb4eac68aca7f
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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