Reaction #42449

Reaction equation

methyl 4-[methyl(methylsulfonyl)amino]-1H-indole-6-carboxylate

potassium hydroxide

iodobutane

→

title compound

1-Butyl-4-[methyl(methylsulfonyl)amino]-1H-indole-6-carboxylic acid

Solvents

DMF

Conditions

Workup

1. 1
   OtherThe mixture was partitioned between water and ethyl acetate
2. 2
   Otherthe layers were separated
3. 3
   Washthe organic layer washed three times with water
4. 4
   DryingThe organic layer was dried over anhydrous sodium sulfate
5. 5
   Filtrationfiltered
6. 6
   Concentrationconcentrated
7. 7
   workup.DISSOLUTIONThe residue was dissolved in methanol (5 mL) to which
8. 8
   workup.ADDITIONwas added 1N NaOH (2 mL)
9. 9
   Temperaturethe mixture heated to 50° C. for 1 h
10. 10
    TemperatureThe mixture was cooled to room temperature
11. 11
    workup.ADDITIONpoured into water
12. 12
    Washwashed with ether
13. 13
    Extractionthe product extracted into ethyl acetate which
14. 14
    Dryingwas dried over anhydrous sodium sulfate
15. 15
    Filtrationfiltered
16. 16
    Concentrationconcentrated to dryness

Procedure

To a mixture of methyl 4-[methyl(methylsulfonyl)amino]-1H-indole-6-carboxylate (0.437 g) in DMF (15 mL) was added potassium hydroxide (0.087 g) and iodobutane (0.34 mL). The mixture was heated to 70° C. for 6 h. then stirred at room temperature for 72 h. The mixture was partitioned between water and ethyl acetate, the layers were separated and the organic layer washed three times with water. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The residue was dissolved in methanol (5 mL) to which was added 1N NaOH (2 mL) and the mixture heated to 50° C. for 1 h. The mixture was cooled to room temperature and poured into water and washed with ether. The aqueous layer was acidified to pH 4 with 1N HCl and the product extracted into ethyl acetate which was dried over anhydrous sodium sulfate, filtered and concentrated to dryness to give 0.377 g of the title compound: 1H NMR (CDCl3) δ 0.973, 1.38, 1.87, 3.01, 3.45, 4.21, 6.71, 7.36, 7.82, 8.18.

Source