Water → HCID 18669077, compound

HRID 1016650Notes

Reaction equation

HRID 1016650 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][C:8]([C:13]1[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=1)=[C:7]2[CH2:20][CH2:21][C:22]([OH:24])=[O:23].I[CH3:26].O>CN(C)C=O>[Cl:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH3:26])[C:8]([C:13]1[CH:14]=[CH:15][C:16]([Cl:19])=[CH:17][CH:18]=1)=[C:7]2[CH2:20][CH2:21][C:22]([OH:24])=[O:23]

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 97977463-[5-chloro-2-(4-chlorophenyl)-1H-indol-3-yl]propanoic Acid

Product 1

HCID 18669077HCID 18669077, compoundYield 72%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydride (60% suspension in mineral oil, 5.98 g) was added in portions to a stirred, cooled (0° C.) solution of 5-chloro-2-(4-chlorophenyl)-1H-indole-3-propanoic acid (Description 30, 10 g, 30 mmol) in dimethylformamide (100 mL) and the mixture was stirred at 0° C. for 30 min. Iodomethane (9 mL) was added in one portion and the mixture was stirred at room temperature for 30 min. Water (1.5 L) was added and the mixture was extracted with ether (3×400 mL). The combined organic fractions were dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was dissolved in methanol (240 mL) and aqueous sodium hydroxide (4M, 60 mL) was added. The mixture was heated under reflux for 1 h., cooled and the pH was adjusted to 1.0 with hydrochloric acid (2M). The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic fractions were dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was triturated with hexane and the solid was collected and dried in vacuo to give the title compound (7.5 g, 72%). 1H NMR (360 MHz, CDCl3) δ 7.58 (1H, d, J 1.8 Hz), 7.44-7.48 (2H, m), 7.18-7.30 (4H, m), 3.53 (3H, s), 2.96-3.00 (2H, m), and 2.54-2.59 (2H, m).

Workup

  1. stirringthe mixture was stirred at room temperature for 30 min
  2. extractionthe mixture was extracted with ether (3×400 mL)
  3. dry with materialThe combined organic fractions were dried (MgSO4)
  4. customthe solvent was evaporated under reduced pressure
  5. dissolutionThe residue was dissolved in methanol (240 mL)
  6. additionaqueous sodium hydroxide (4M, 60 mL) was added
  7. temperatureThe mixture was heated
  8. temperatureunder reflux for 1 h.
  9. temperaturecooled
  10. customThe layers were separated
  11. extractionthe aqueous layer was extracted with ethyl acetate
  12. dry with materialThe combined organic fractions were dried (MgSO4)
  13. customthe solvent was evaporated under reduced pressure
  14. customThe residue was triturated with hexane
  15. customthe solid was collected
  16. customdried in vacuo

Sources & evidence

ORD record
ord-17fb4dde566242e3862b8cac097b81a7
Source dataset
uspto-grants-2002_11
Patent number
US06476045B2

Reaction notes

Loading…