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

HRID 1054758Notes

Reaction equation

HRID 1054758 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]([CH:19]2[O:24][CH2:23][C:22](=[O:25])[NH:21][CH2:20]2)=[CH:15][CH:14]=1.CC(=CC)C.Cl([O-])=[O:32].[Na+].O.OP([O-])(O)=O.[Na+].S([O-])([O-])=O.[Na+].[Na+]>C(#N)C.CC(O)(C)C.O>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([OH:32])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:13]1[CH:18]=[CH:17][C:16]([CH:19]2[O:24][CH2:23][C:22](=[O:25])[NH:21][CH2:20]2)=[CH:15][CH:14]=1

Participants

9

Reactant 5

HCID 105532-Methyl-2-buteneHCID 24437Sodium SulfiteHCID 516949Sodium Phosphate, Monobasic, MonohydrateHCID 23668197Sodium ChloriteHCID 866987506-chloro-5-[4-(5-oxomorpholin-2-yl)phenyl]-1H-indole-3-carbaldehyde

Product 1

HCID 866987516-chloro-5-[4-(5-oxomorpholin-2-yl)phenyl]-1H-indole-3-carboxylic acidYield 26%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6386tert-ButanolSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 6-chloro-5-[4-(5-oxomorpholin-2-yl)phenyl]-1H-indole-3-carbaldehyde (150 mg, 0.42 mmol) in acetonitrile (5 mL) and t-BuOH (5 mL) was added 2-methyl-2-butene (2.9 g, 42 mmol). The mixture was cooled to 0° C. with ice bath. Sodium chlorite (1.15 g, 12.7 mmol) and sodium phosphate monobasic hydrate (1.75 g, 12.7 mmol) were dissolved in water (5 mL). The aqueous was added to the organic solution and the mixture was allowed to warm to room temperature. The reaction mixture was stirred at room temperature for 48 hours. A solution of sodium sulfite was added slowly to the stirring mixture. The reaction mixture was allowed to stir 1 hour. Then the organics were removed under reduced pressure. The aqueous layer was extracted with ethyl acetate (10 mL×3). The combined organic layers was dried over sodium sulfate, filtered, and concentrated in vacuo to give a brown residue. The residue was purified by reverse phase HPLC to give the title compound (40 mg, 26% yield) as an off-white solid. MS (ES+) 371.0 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ 12.00 (s, 1H), 8.20 (s, 1H), 8.10 (s, 1H), 7.93 (s, 1H), 7.63 (s, 1H), 7.48 (d, 2H), 7.44 (d, 2H), 4.65 (m, 1H), 4.22 (s, 2H), 3.46 (m, 2H).

Workup

  1. additionThe aqueous was added to the organic solution
  2. temperatureto warm to room temperature
  3. stirringto stir 1 hour
  4. customThen the organics were removed under reduced pressure
  5. extractionThe aqueous layer was extracted with ethyl acetate (10 mL×3)
  6. dry with materialThe combined organic layers was dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give a brown residue
  10. customThe residue was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-90cc4651239c4044a6ecd83f8d1f247d
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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