Reaction #5696

Reaction equation

sodium amide

ammonia

benzyl chloride

5-methylindole

ammonia

→

1-benzyl-5-methylindole

Yield 53.0%

Solvents

ether

ether

Conditions

Workup

1. 1
   workup.STIRRINGThe mixture was stirred for two hours
2. 2
   Otherto evaporate overnight
3. 3
   WashThe inside of the flask was washed down with MeOH
4. 4
   workup.ADDITIONThen 150 ml of H2O was added
5. 5
   OtherThe layers were separated
6. 6
   ExtractionThe aqueous layer was extracted with 100 ml of ether
7. 7
   WashThe combined ether phases were washed with 50 ml of brine
8. 8
   Dryingdried over MgSO4
9. 9
   OtherEvaporation of the solvent
10. 10
    workup.WAITleft 9.41 g of oil
11. 11
    OtherThe oil was chromatographed on a 700 g column of silica gel
12. 12
    WashThe column was eluted with 30% CH 2 Cl2 -Skellysolve B and 200 ml fractions
13. 13
    Otherwere collected

Procedure

To a stirred mixture of sodium amide (prepared from 0.9 g 39.13 mmoles of sodium) and ca 100 ml of liquid ammonia was added a solution of 5.08 g (38.73 mmoles) of 5-methylindole in 100 ml of ether during 5 minutes. The mixture was stirred for 1.5 hours. Then a solution of 5.15 g (40.68 mmoles) of benzyl chloride in 100 ml of ether was added during 10 minutes. The mixture was stirred for two hours. The ammonia was allowed to evaporate overnight. The inside of the flask was washed down with MeOH. Then 150 ml of H2O was added. The layers were separated. The aqueous layer was extracted with 100 ml of ether. The combined ether phases were washed with 50 ml of brine and dried over MgSO4. Evaporation of the solvent left 9.41 g of oil. The oil was chromatographed on a 700 g column of silica gel. The column was eluted with 30% CH 2 Cl2 -Skellysolve B and 200 ml fractions were collected. The fractions were assayed by silica gel tlc (2×8") (25% CH2Cl2 -Skellysolve B). Fractions 12-17 were combined giving 4.52 g (53%) of 1-benzyl-5-methylindole as a yellow-green oil.

Source