Reaction #6839

Reaction equation

1-methoxy-2,3-dimethyl-4-nitro-benzene

N,N-dimethylformamide dimethylacetal

triethylamine

→

5-methoxy-4-methyl-indole

Solvents

N,N-dimethylformamide

Conditions

Workup

1. 1
   Temperatureto reflux for 3 days under nitrogen
2. 2
   OtherThe volatiles were removed in vacuo
3. 3
   workup.DISSOLUTIONthe resulting residue was dissolved in 40 mL of a 1:1 mixture of methanol and tetrahydrofuran
4. 4
   workup.ADDITIONRaney nickel (50% slurry in water, 1 mL) was added to the solution
5. 5
   workup.ADDITIONhydrazine hydrate (2.7 mL) was added dropwise
6. 6
   FiltrationThe reaction mixture was filtered through a bed of celite
7. 7
   OtherThe product was purified by column chromatography (30% ethyl acetate in hexanes)

Procedure

A solution of 1-methoxy-2,3-dimethyl-4-nitro-benzene (5.0 g), N,N-dimethylformamide dimethylacetal (7.4 mL) and triethylamine (0.10 mL) in 25 mL of N,N-dimethylformamide was heated to reflux for 3 days under nitrogen. The volatiles were removed in vacuo and the resulting residue was dissolved in 40 mL of a 1:1 mixture of methanol and tetrahydrofuran. Raney nickel (50% slurry in water, 1 mL) was added to the solution, then hydrazine hydrate (2.7 mL) was added dropwise and the mixture was stirred for 40 min under nitrogen. The reaction mixture was filtered through a bed of celite and the filtrate was reduced in vacuo. The product was purified by column chromatography (30% ethyl acetate in hexanes) to yield 1.5 g of pure 5-methoxy-4-methyl-indole.

Source