2-Methyl-2-butene → 6-Chloro-5-phenyl-1H-indole-3-carboxylic acid

HRID 1054567Notes

Reaction equation

HRID 1054567 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]=[CH:15][CH:14]=1.CC(=CC)C.Cl([O-])=[O:25].[Na+].O.OP([O-])(O)=O.[Na+]>CC#N.C(O)(C)(C)C.O>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([OH:25])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

8

Reactant 4

HCID 105532-Methyl-2-buteneHCID 516949Sodium Phosphate, Monobasic, Monohydrate2×HCID 23668197Sodium Chlorite2×HCID 866985726-Chloro-5-phenyl-1H-indole-3-carbaldehyde

Product 1

HCID 866985736-Chloro-5-phenyl-1H-indole-3-carboxylic acidYield 31.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6386tert-ButanolSolvent

Procedure

To a solution of 6-chloro-5-phenyl-1H-indole-3-carbaldehyde (90 mg, 0.35 mmol) in MeCN (4 mL), tert-butanol (4 mL) and 2-methyl-2-butene (4 mL, 27.5 mmol) at 0° C. was added a solution of sodium chlorite (327 mg, 4.88 mmol) and sodium phosphate monobasic hydrate (761 mg, 4.88 mmol) in water (4 mL) dropwise. The ice bath was removed and the solution was stirred at room temperature. After 6 hours, additional sodium chlorite (327 mg, 4.88 mmol) and sodium phosphate monobasic hydrate (761 mg, 4.88 mmol) were added as solids and the resulting solution was stirred at room temperature for an additional 14 hours. The reaction mixture was concentrated in vacuo and the aqueous residue was extracted with EtOAc (30 mL). The organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuo. The crude material was purified by reverse phase HPLC to afford the title compound (30.0 mg, 31%) as a white solid. MS (ES+) 271.9 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ 12.13 (br. s., 1 H), 11.96 (s, 1 H), 8.09 (s, 1 H), 7.93 (s, 1 H), 7.62 (s, 1 H), 7.48-7.38 (m, 5 H).

Workup

  1. customThe ice bath was removed
  2. stirringthe resulting solution was stirred at room temperature for an additional 14 hours
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. extractionthe aqueous residue was extracted with EtOAc (30 mL)
  5. washThe organic layer was washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-9b31f04807604b84b58a11cc6838e978
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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