Sodium Hydroxide → 6-chloro-5-(4-(2-hydroxypropan-2-yl)-3-methoxyphenyl)-1H-indole-3-carboxylic acid

HRID 1054704Notes

Reaction equation

HRID 1054704 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]([OH:24])([CH3:23])[CH3:22])=[C:17]([O:25][CH3:26])[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]([OH:24])([CH3:23])[CH3:22])=[C:17]([O:25][CH3:26])[CH:16]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 86698700methyl 6-chloro-5-(4-(2-hydroxypropan-2-yl)-3-methoxyphenyl)-1H-indole-3-carboxylate

Product 1

HCID 866987026-chloro-5-(4-(2-hydroxypropan-2-yl)-3-methoxyphenyl)-1H-indole-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

To a flask containing methyl 6-chloro-5-(4-(2-hydroxypropan-2-yl)-3-methoxyphenyl)-1H-indole-3-carboxylate (24.0 mg, 0.064 mmol) was added methanol (0.64 mL), and 1N NaOH (0.19 mL, 0.19 mmol). The reaction was heated at 70° C. for 18 h. The reaction was then concentrated to remove most of the methanol and then dissolved in water. 0.19 mL of 1 N HCl was then added to the mixture to pH 2. Solid precipitated out. The solid was collected with a Buchner funnel and washed with water to provide crude 6-chloro-5-(4-(2-hydroxypropan-2-yl)-3-methoxyphenyl)-1H-indole-3-carboxylic acid. The crude material was purified by reverse phase chromatography to give the title compound. MS (ES−) 358.1 (M−H)−: Retention time: 1.40 min. Column: Waters XBridge dC18 4.6×50 mm, 5 μm. Modifier: NH4OH 0.03%. Gradient: 95% H2O/5% MeCN linear to 5% H2O/95% MeCN over 4.0 min, HOLD at 5% H2O/95% MeCN to 5.0 min. Flow: 2.0 mL/min.

Workup

  1. concentrationThe reaction was then concentrated
  2. customto remove most of the methanol
  3. dissolutiondissolved in water
  4. addition0.19 mL of 1 N HCl was then added to the mixture to pH 2
  5. customSolid precipitated out
  6. customThe solid was collected with a Buchner funnel
  7. washwashed with water
  8. customto provide crude 6-chloro-5-(4-(2-hydroxypropan-2-yl)-3-methoxyphenyl)-1H-indole-3-carboxylic acid
  9. customThe crude material was purified by reverse phase chromatography

Sources & evidence

ORD record
ord-c2fd75d3beca4c28af019321bc228d93
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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