2-Methyl-2-butene → Indole-3-Carboxylic Acid

HRID 1054626Notes

Reaction equation

HRID 1054626 reaction equation
Cl[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]=1C1C=CC(OCC(C)(C)CO)=CC=1.CC(=CC)C.Cl([O-])=[O:32].[Na+].OP([O-])(O)=O.[Na+]>C(#N)C.C(OCC)(=O)C.O.C(O)(C)(C)C>[NH:8]1[C:9]2[C:5](=[CH:4][CH:3]=[CH:2][CH:10]=2)[C:6]([C:11]([OH:12])=[O:32])=[CH:7]1

Participants

9

Reactant 4

HCID 105532-Methyl-2-buteneHCID 23668197Sodium ChloriteHCID 23672064Monosodium phosphateHCID 86698628HCID 86698628, compound

Product 1

HCID 69867Indole-3-Carboxylic AcidYield 73%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6386tert-ButanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 6-chloro-5-[4-(3-hydroxy-2,2-dimethylpropoxy)phenyl]-1H-indole-3-carbaldehyde (60 mg, 0.17 mmol) in acetonitrile (3 mL) was added tert-butanol (3 mL), water (3 mL) and 2-methyl-2-butene (1.38 mL). The reaction mixture was stirred for 2 min then treated with sodium chlorite (338 mg, 3.76 mmol) and sodium phosphate monobasic (787 mg, 5.04 mmol). The mixture was stirred at room temperature overnight. The reaction was quenched with sodium sulfite and concentrated in vacuo to give a residue, which was dissolved with ethyl acetate (50 mL), washed with brine (3×15 mL), dried over sodium sulfate and concentrated in vacuo. The residue was purified by prep-HPLC to give 2,2-dimethylpropoxy)phenyl]-1H-indole-3-carboxylic acid (20 mg, 32%) as an off-white solid. MS (ES−) 372.1 (M−H)−. 1H NMR (400 MHz, CD3OD) δ 8.01 (s, 1H), 7.99 (s, 1H) 7.56 (s, 1H), 7.35 (d, 2H), 6.98 (d, 2H), 3.80 (s, 2H), 3.49 (s, 2H), 1.04 (s, 6H).

Workup

  1. stirringThe mixture was stirred at room temperature overnight
  2. customThe reaction was quenched with sodium sulfite
  3. concentrationconcentrated in vacuo
  4. customto give a residue, which
  5. washwashed with brine (3×15 mL)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-c464a0b9e3614bd2b039777fa242cd15
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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