2-Methyl-2-butene → HCID 67372252, compound

HRID 1678142Notes

Reaction equation

HRID 1678142 reaction equation
[Cl:1][C:2]1[N:3]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:4]2[C:9]([C:10]=1C=O)=[CH:8][CH:7]=[CH:6][CH:5]=2.CC(=CC)C.Cl([O-])=O.[Na+].[OH2:28].P([O-])(O)(O)=O.[Na+].[O:35]1[CH2:40]COCC1>O.C(OCC)(=O)C>[Cl:1][C:2]1([C:40]([OH:35])=[O:28])[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

8

Reactant 5

HCID 105532-Methyl-2-buteneHCID 312751,4-DioxaneHCID 3147932-chloro-1-phenyl-1H-indole-3-carbaldehydeHCID 516949Sodium Phosphate, Monobasic, Monohydrate3×HCID 23668197Sodium Chlorite3×

Product 1

HCID 67372252HCID 67372252, compoundYield 77.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a vigorously stirred solution of 2-chloro-1-phenyl-1H-indole-3-carboxaldehyde (4.0 g, 15.6 mmol), 2 M 2-methyl-2-butene (74 mL, 148 mmol) in dioxane (58 mL) at 25° C. is added dropwise over 30 min a solution of sodium chlorite (7.8 g, 86 mmol) and sodium dihydrogenphosphate hydrate (7.8 g, 56 mmol) in water (40 mL). After 2.5 hr, more sodium chlorite (1.92 g, 21.2 mmol) and sodium dihydrogenphosphate hydrate (1.92 g) are added. After 2.5 hr, more sodium chlorite (0.96 g, 10.6 mmol) and sodium dihydrogenphosphate hydrate (0.96 g) are added. After a total reaction time of 6.5 hr, ethyl acetate (100 mL) is added and stirring continued for 45 min. The aqueous layer is separated and extracted with ethyl acetate (2×60 mL). The combined ethyl acetate layer and extracts is concentrated to approximately 80 mL and then extracted with 1% aq. sodium hydroxide (3×150 mL). The combined aqueous extract is made acidic with conc. hydrochloric acid. The resulting solids are collected by filtration, washed with water and crystallized from 2-propanol to afford 2-chloro-1-phenyl-1H-indole-2-carboxylic acid (3.28 g, 77.5% yield) as a pale yellow solid. NMR (CDCl3) 8.30 (1H, d), 7.60 (3H, m), 7.41 (2H, d), 7.38 (1H, t), 7.23 (1H, m), 7.10 (1H, d).

Workup

  1. waitAfter 2.5 hr
  2. waitcontinued for 45 min
  3. customThe aqueous layer is separated
  4. extractionextracted with ethyl acetate (2×60 mL)
  5. concentrationThe combined ethyl acetate layer and extracts is concentrated to approximately 80 mL
  6. extractionextracted with 1% aq. sodium hydroxide (3×150 mL)
  7. extractionThe combined aqueous extract
  8. filtrationThe resulting solids are collected by filtration
  9. washwashed with water
  10. customcrystallized from 2-propanol

Sources & evidence

ORD record
ord-1eb176a33a7c43bd8f9ebceab42ccb46
Source dataset
uspto-grants-2011_08
Patent number
US08008491B2

Reaction notes

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