DE2906551C3 - - Google Patents

Description

CH ₂ -N

CH ₃

(H)

CH ₃

wherein

R and Ri have the meaning given above

and R2 stands for a hydrogen atom or a

Alkyl, aryl or aralkyl radical with up to

7 carbon atoms, characterized in that a corresponding 2-dimethylaminoindole of the general formula II with hydrogen in the presence of Raney nickel at temperatures above room temperature in an inert solvent hydrogenated

The invention relates to the subject matter of the claim.

As alkyl radicals, for example, the methyl, Called ethyl, propyl, butyl, tert-butyl and sec-butyl radicals

The compounds which can be prepared by the process according to the invention are intermediates for Production of valuable biologically active compounds, such as. B. ß-receptor blockers.

It is known that 4-hydioxy-2-met lylindol in a three-step process from 4-benzyloxy-2-dimethylaminomethylindole by reaction with methyl iodide to ammonium iodide, subsequent reduction with lithium aluminum hydride to 4-benzyloxy-2-methylindole and reductive cleavage of the benzyl ether residue with hydrogen / palladium catalysts can be produced

The known method has the disadvantage that it takes place over several stages and only unsatisfactory Yields.

The object of the invention was to provide a method that runs over fewer stages and delivers higher yields.

The course of the reaction according to the invention was surprising in that it would have been expected that hydrogenated products would also be formed in the core, as in the prolonged hydrogenation (over 3-4 days) with hydrogen / palladium-carbon (Seemann et aL, HeIv. Chem. Acta, 54 (1971) 2411).

The inventive method is carried out so that the starting material in an inert Solvent dissolves and hydrogenated at temperatures above room temperature

Suitable solvents are those that do not react with the reactants and the starting material keep in solution, such as aüphatic alcohols, z. B. methanol and ethanol, aromatic hydrocarbons, z. B. benzene and toluene, and aliphatic coal substances, e.g. B. hexane.

The temperature is above room temperature and can reach the temperature of the boiling reaction mixture. A preferred temperature range is 30 to 6O ⁰ C

The Raney nickel used can be of any quality; h, it doesn't need to be fresh before the reaction to be made.

The hydrogenation can be carried out either at normal pressure or at slightly increased pressure.

The following examples are intended to explain the process according to the invention.

example 1

10 g of 4-benzyloxy-2-dimethylaminomethylindole in 100 ml of methanol are ^{hydrogenated with 15 g of Raney nickel at 50 °} C. until hydrogen uptake is complete. After filtration, the solvent is concentrated in vacuo and the oily residue is crystallized from a little methylene chloride 5.0 g (= 95% dTh.) of 4-hydroxy-2-methylindole as colorless crystals of melting point 124-126 ⁰ C. UV _265: 8250th

Example 2

10 g of 4-benzyloxy-2-dimethylaminomethylindole in 100 ml of toluene are ^{hydrogenated at 30 °} C. with 20 ml of Raney nickel under normal pressure. After hydrogen uptake is complete, the catalyst is filtered off, evaporated and the residue is filtered through silica gel

■ is obtained 4.6 g (88% of theory) of 4-hydroxy-2-methylindole as colorless crystals of melting point 122-124 ⁰ C. UV "": 8100th

Example 3

10 g of 4-benzyloxy-2-dimethylaminopropyl. ~ ÜnomethylindoI in 350 ml propanol was hydrogenated at 6O ⁰ C and 10 ml of Raney nickel at 1.2 bar until the uptake of hydrogen ended. After filtration, it is concentrated and crystallized from methylene chloride. 43 g (93% of theory) of 4-hydroxy-2-methylindole as colorless crystals of melting point 123-125 ⁰ C. UVmj: 8300th

Example 4

10 g of 4-hydroxy-2-dimethylaminomethylindole in 200 ml of ethanol are slowly added to a stirred suspension of 10 g of Raney nickel in 50 ml of ethanol 50 ° C under a hydrogen atmosphere. When the reaction has ended, it is filtered and evaporated

hj and the oily residue filtered through silica gel. 7.1 g (92% of theory) of 4-hydroxy-2-methylindole with a melting point of 125-127 ° C. are obtained. UV ₂₆₅ : 8300.

3 4

Example 5

1 g of l-ethyl- ^ methoxy ^ -dimethylaminomethyl-S- concentrated in vacuo and the oily residue from methyl

methylindole in 50 ml of methanol are crystallized with 3 g of Raneylene chloride. 0.73 g of 4-hydroxy-

Nickel at 50 ⁰ C until saturation with hydrogen hy- 5 l-ethyl-Z5-dimethylindole as colorless crystals from

driert After filtration of the reaction mixture in melting point 111-113 ⁰ C.

Example 6

5 g of 4-benzyloxy-2-dimethylaminomethyl-6-methyI- ι ο 3 g of Raney nickel at 60 "until the end of the hydrogen

indole (produced from 4-benzyIoxy-2-dimethyIamino uptake hydrogenated. Obtained after filtration and concentration

carbonyl-6-methylindole according to DE-OS 26 26 890 by adding 2.5 g (87% of theory) of 4-hydroxy-2,6-dimethylindole as

Reduction with lithium aluminum hydride in tetrahydro-oily residue,

furan) in 150 ml of i-PropanoI are in the presence of UVW. 8000.

Claims (1)

Claim: Process for the preparation of 4-hydroxy-2-methylindoles of the general formula I. wherein R. a hydrogen atom or a lower alkyl radical with up to 3 carbon atoms and denotes a hydrogen atom or an alkyl radical with up to 5 carbon atoms, from corresponding 2-dimethylaminomethylindoles of the general formula II