2-Methyl-2-butene → 6-chloro-5-(3-methoxyphenyl)-1H-indole-3-carboxylic acid

HRID 1054644Notes

Reaction equation

HRID 1054644 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][CH:16]=[C:15]([O:19][CH3:20])[CH:14]=1.CC(=CC)C.Cl([O-])=[O:27].[Na+].P([O-])(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:27])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[CH:14]=1

Participants

7

Reactant 4

HCID 105532-Methyl-2-buteneHCID 23668197Sodium ChloriteHCID 23672064Monosodium phosphateHCID 866986466-chloro-5-(3-methoxyphenyl)-1H-indole-3-carbaldehyde

Product 1

HCID 866986476-chloro-5-(3-methoxyphenyl)-1H-indole-3-carboxylic acidYield 38%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 22050040Acetonitrile tert-butanolSolvent

Procedure

To a solution of 6-chloro-5-(3-methoxyphenyl)-1H-indole-3-carbaldehyde (100 mg, 0.35 mmol) in ACN/t-butanol=1/1 (4 mL) was added 2-methyl-2-butene (1 mL) at 0° C. and stirred 10 min. Then an aqueous solution of sodium chlorite (315 mg, 3.5 mmol) and sodium dihydrogen phosphate (480 mg, 3.5 mmol) in water (1 mL) was added to the system dropwise. The reaction was stirred at room temperature for 10 h. The reaction was quenched with sodium sulfite. The mixture was partitioned between DCM and water. The combined organics were dried and concentrated to give a residue, which was purified by reverse phase HPLC to give the title compound (40 mg, 38%) as a white solid. MS (AP−) 300.1 (M−1)−. 1H NMR (400 MHz, CD3OD) δ 8.01 (s, 1 H), 8.00 (s, 1 H), 7.58 (s, 1 H), 7.33 (t, 1 H), 7.01-6.97 (m, 2 H), 6.93 (dd, 1 H), 3.84 (m, 1 H).

Workup

  1. stirringThe reaction was stirred at room temperature for 10 h
  2. customThe reaction was quenched with sodium sulfite
  3. customThe mixture was partitioned between DCM and water
  4. customThe combined organics were dried
  5. concentrationconcentrated
  6. customto give a residue, which
  7. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-df6fb648eaad4b1cb4fe86a7d9e06e54
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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