2-Methyl-2-butene → 6-chloro-5-[4-(2-hydroxyethyl)phenyl]-1H-indole-3-carboxylic acid

HRID 1054737Notes

Reaction equation

HRID 1054737 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:11]=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:13]1[CH:18]=[CH:17][C:16]([CH2:19][CH2:20][OH:21])=[CH:15][CH:14]=1.CC(=CC)C.Cl([O-])=[O:28].[Na+].O.OP([O-])(O)=O.[Na+]>C(#N)C.C(O)(C)(C)C.O>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([OH:28])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:13]1[CH:18]=[CH:17][C:16]([CH2:19][CH2:20][OH:21])=[CH:15][CH:14]=1

Participants

8

Reactant 4

HCID 105532-Methyl-2-buteneHCID 516949Sodium Phosphate, Monobasic, MonohydrateHCID 23668197Sodium ChloriteHCID 866987366-chloro-5-[4-(2-hydroxyethyl)phenyl]-1H-indole-3-carbaldehyde

Product 1

HCID 717678346-chloro-5-[4-(2-hydroxyethyl)phenyl]-1H-indole-3-carboxylic acidYield 25%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6386tert-ButanolSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of 6-chloro-5-[4-(2-hydroxyethyl)phenyl]-1H-indole-3-carbaldehyde (150 mg, 0.50 mmol) in acetonitrile (5 mL) and tert-butanol (5 mL) was added 2-methyl-2-butene (5 mL). The reaction mixture was cooled to 0° C. and treated with a solution of sodium chlorite (900 mg, 10.0 mmol) and sodium phosphate monobasic hydrate (1.4 g, 10 mmol) in water (5 mL) dropwise via additional funnel. Then ice bath was removed, and the reaction was stirred at room temperature for 20 hours. The solvent was removed in vacuo to give a residue, which was purified by pre-HPLC (Kromasil Eternity-5-C18 150×30 mm×5 μm Mobile phase: from 26% MeCN in water (0.1% TFA) to 41% MeCN in water (0.1% TFA); Wavelength: 220 nm Flow rate: 30 mL/min) to give 6-chloro-5-[4-(2-hydroxyethyl)phenyl]-1H-indole-3-carboxylic acid (35 mg, 25% yield) as a white solid. MS (ES+) 337.9 (M+Na)+. 1H NMR (400 MHz, CD3OD) δ 8.01-7.99 (m, 2 H), 7.57 (s, 1 H), 7.37 (d, 2 H), 7.30 (d, 2 H), 3.80 (t, 2 H), 2.91 (t, 2 H).

Workup

  1. customThen ice bath was removed
  2. customThe solvent was removed in vacuo
  3. customto give a residue, which
  4. customwas purified by pre-HPLC (Kromasil Eternity-5-C18 150×30 mm×5 μm Mobile phase: from 26% MeCN in water (0.1% TFA) to 41% MeCN in water (0.1% TFA); Wavelength: 220 nm Flow rate: 30 mL/min)

Sources & evidence

ORD record
ord-22c0e6b3e4794900a2936f149947e297
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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