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

HRID 338361Notes

Reaction equation

HRID 338361 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 1N 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 1N 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-f7211121931f489089b504e074aaa67e
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

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