NZ199468A - Process for the preparation of 4-aminobutyramide (gabamide) - Google Patents

Abstract

1. A process for the preparation of 4-aminobutyramide characterized in that 4-nitrobutyramide is reduced by hydrogenation in the presence of a catalyst.

Description

New Zealand Paient Spedficaiion for Paient Number 1 99468 1 99468 If-1 >%! I >23.

Priority Dat&(s): .

CompSste Specification Fi5ed.

Class: .CP.lC.m -gl" MAV 19i 'hs8 PubHcctxri L'^ts: UvJ NEW ZEALAND N/347 25- PATENTS ACT 1953 PATENTS FORM NO. 3 COMPLETE SPECIFICATION "PROCESS FOR THE PREPARATION OF 4-AMINOBUTYRAMIDE" WE, SYNTHELABO, a French Body Corporate, of 58 rue de la Glaciere, 75621 Paris Cedex 13, France, hereby declare the invention for which we pray that a patent may be granted to us and the method by which it is to be performed, to be particularly described in and by the following statement: (followed by page la) \ 1 9946 - la-DESCRIPTION "PROCESS FOR THE PREPARATION OF 4-AMINOBUTYRAMIDE" The present invention relates to a new process for the preparation of gabamide.

Various preparations of gabamide, or 4-amino-butyramide, have already been described in the literature: in particular, the article in Angew.

Chem. Int. Ed. 19_ (1980), page 627, describes the selective hydrogenation of 3-cyanopropionamide in the presence of hydrogen chloride.

The present invention relates to an economical process which leads to gabamide with a very good yield. The process of the invention is illustrated in the following scheme: nh4oh/nh4ci N02-CH2-CH2-CH2-C00Alkyl ^NC>2-CH2-CH2-CH2-CONH2 [h]/hci NH2-CH2-CH2-CH2-CONH2 The starting compound, namely an alkyl 4-nitrobutanoate, more particularly methyl 4-nitrobutanoate, is described in J. Org. Chem. 1962, 1609. 1 9 94 The first step of the process consists in converting the alkyl 4-nitrobutanoate to 4-nitrobutyramide by any suitable means for converting an ester to an amide, for example by aminolysis, 5 in particular in the presence of ammonia solution and ammonium chloride. 4-Nitrobutyramide is known and has been prepared by a different method, also described in J. Org. Chem. 1962, 1609.

The reduction of 4-nitrobutyramide to 10 4-aminobutyramide, which is the key step in the process of the present invention, is carried out by any suitable means for reducing the nitro radical to the amino radical. It can be carried out, in particular, by hydrogenation in the presence of a catalyst and an 15 acid (preferably an inorganic acid), under a pressure ranging, for example, from 1 to 10 bars, and at a temperature ranging from 0 to 50°C.

The hydrogenation catalysts are, for example, platinum oxide (Pt02) or Raney nickel. 20 The preferred acid is hydrochloric acid.

The following Example illustrates the invention. 1. 4-NITROBUTYRAMIDE In a 500 ml Erlenmeyer flask, 15 g (0.102 mol) 25 of methyl 4-nitrobutanoate are introduced into 60 ml of ammonia solution (density: 0.92) and 1.5 g (0.03 mol) of 19 94 ammonium chloride. The mixture is stirred overnight by means of a magnetic stirrer at the temperature of the laboratory. The solution is concentrated in vacuo at 45-50°C. The residue is taken up in 200 ml of ethyl acetate and the solution is filtered to remove the salts therefrom. A small amount of activated charcoal is added, the mixture is filtered and the solution is concentrated to a third of the initial volume. The product crystallises in the form of white crystals.

Melting point = 89°C (Kofler); 88-89°C (Tottoli: l°C/minute).

Yield: 13.47 g (100%).

The IR and NMR spectra are consistent. 2. 4-AMINOBUTYRAMIDE (HYDROCHLORIDE) 0.25 g (1.9 millimols) of 4-nitrobutyramide, 20 ml of methanol, 5 ml of IN hydrochloric acid and 0.0 2 g of platinum oxide (Pt02) are introduced into a Parr bomb. The mixture is agitated for 2 hours at 20°C under hydrogen (4 bars). The platinum is filtered off and the solution is concentrated. The residual mass is taken up in 5 ml of ethanol. 20 ml of ethyl acetate are then added to the solution. The crystalline product is filtered off and dried.

Melting point = 139-140°C (Kofler); 138°C (Tottoli: l°C/minute).

Yield: 0.218 g (98%). 1 994 _ 4 - The IR and NMR .spectra are identical to those of the authentic product.

The process of the invention makes it possible to obtain gabamide with a very good yield and economically, gabamide being a product known for its psychotropic properties and a starting material for syntheses which lead to benzylidene derivatives having very valuable pharmacological properties. 1994

Claims (11)

WHAT WE CLAIM IS:

1. Process for the preparation of 4-aminobutyramide which comprises reducing the nitro radical of 4-nitrobutyramide to the primary amino radical.

2. Process according to claim 1 in which r reduction of the nitro radical is effected by hydrogenation in the presence of a catalyst.

3. Process according to claim 2 in which the catalyst is platinum oxide or Raney nickel.

4. Process according to claim 3 in which the hydrogenation is carried out in the presence of platinum oxide and an acid.

5. Process according to claim 4 in which the acid is hydrochloric acid.

6. Process according to any one of claims 2 to 5 in which the catalytic hydrogenation of 4-nitrobutyramide is carried out under a pressure ranging from 1 to 10 bars and at a temperature ranging from 0 to 50°C.

7. Process according to claim 1 in which the 4-nitrobutyramide is obtained from an alkyl 4-nitrobutanoate. 1 99468 - 6 -

8. Process according to claim 7 in which an alkyl 4-nitrobutanoate is converted to 4-nitrobutyramide by aminolysis.

9. Process according to claim 8 in which the aminolysis is carried out using ammonia solution and ammonium chloride.

10. Process for the preparation of 4-aminobutyramide according to claim 1 substantially as described in the foregoing Example.

11. 4-Aminobutyramide when prepared by the process claimed in any one of the preceding claims. SVNrrH^ lR So By Hts/thelr authorised Agents., A. J. PARK & SON.