2-Alkoxyphenoxyethanamines are known compounds. They are used among others as starting material for the synthesis of pharmaceutical active substances like for example Carvedilol as described in US 4,503, 067 and Tamsulosin as described in US 4,731, 478.

CH 383 998 discloses a synthesis of 2-Alkoxyphenoxyethanamines in which liquid ammonia is reacted with 2-Methoxyphenoxyethylbromide in methanol. The mixture is heated for ten hours in an autoclave. This method often leads to di-and tri-substituted amines as side products.

Unsatisfying yields, complicated isolation procedure and the use of liquid ammonia makes this process very costly.

US 3,474, 134 discloses a synthesis of 2-Alkoxyphenoxyethanamines in which three steps are involved. In addition, halogenated substances as well as the toxic, corrosive and inflammable substance hydrazin are employed. This makes the synthesis not convenient for production in larger scale.

US 3,412, 154 discloses a two-step synthesis of 2- Alkoxyphenoxyethanamines in which the harmful substance chloroacetonitrile is used and a pressurised catalytic hydrogenation by raney cobalt catalyst is required. This makes the synthesis dangerous and costly as well.

An industrial process for the synthesis of 2-Alkoxyphenoxyethanamines which is cheap and easy to operate, is a long felt need for those skilled in the art.

The object of the present invention is therefore to provide a process for the,. industrial production of 2-Alkoxyphenoxyethanamines which is cheap and easy to operate.

In carrying out this object, the present invention provides the new chemical entity 2-Alkoxyphenoxyethylacetamide as the only intermediate in the process for producing a 2-Alkoxyphenoxyethanamine. By employing 2- Alkoxyphenoxyethylacetamide as an easily available intermediate, the number of process steps is reduced with advantage and the raw material employed is easy to obtain and to handle.

In the present invention, to produce 2-Alkoxyphenoxyethanamine, first the 2-Alkoxyphenoxyethylacetamide has to be produced by a process, using the reaction of an ortho substituted phenol with a 2-Alkyloxazoline. This reaction only comprises the use of cheap, harmless and easily available raw materials and makes the process for producing 2- Alkoxyphenoxyethanamine suitable for production in industrial scale.

The process to synthesize 2-Alkoxyphenoxyethylacetamide uses an ortho substituted phenol which has the formular where R is selected from the group consisting of methyl or ethyl. As a convenient second educt for the process, 2-Alkyloxazoline, which has the formular

is used. R'is selected from the group consisting of methyl or ethyl.

In a preferred embodiement of the invention, it was found that the reaction of these two educts can be carried out either without solvents at 130- 200°C or in high boiling solvents. The possibility of the performing this reaction either without solvents or with solvents easy to handle is clearly an advantage of the present invention and reduces the costs of an industrial production process.

The reaction of the two educts leads to the 2- Alkoxyphenoxyethylacetamide, which is a new chemical entity. The acetamide can be easily isolated by pouring the reaction mixture into water and collecting the solid residue. The acetamide has the formular

where R and R'are each selected from the group consisting of methyl or ethyl. By using the before mentioned educts, surprisingly no further purification of the obtained 2-Alkoxyphenoxyethylacetamide is necessary.

This acetamide is than used further in the present inventive process.

The second step comprises hydrolyzation of the acetamide with water and is obtained in the presence of organic or mineralic acids such as hydrochloric acid or sulfuric acid to give a 2-Alkoxyphenoxyethanamine.

Surprisingly, cleavage at the ether oxygen or aromatic ring substitution does not appear, if hydrolysis of the acetamide is performed in the presence of hydrochloric acid. The use of phosphoric acid would lead to process water containing phosphate salts. For reasons of environmental protection, these phosphate salts have to be removed from the process water, which again causes costs. In contrast to one, of the methods of the state of the art, the reactions may be conducted under atmospheric pressure. Another advantage of the present invention is the absence of a catalyst, as was necessary in one of the methods described in the state of the art.

The present invention comprises the new chemical entity 2- Methoxyphenoxyethylacetamide, in particular as intermediate compound in the process for production of 2-Alkoxyphenoxyethanamine. It also comprises the use of an ortho substituted phenol for the reaction with an 2-Alkyloxazoline to give the acetamide. It further comprises the use of the 2-Alkyloxazoline for the reaction with the ortho substituted phenol to give the acetamide intermediate and the use of the acetamide intermediate in a hydrolysis reaction to give a 2-Alkoxyphenoxyethanamine.

The invention will be further illustrated by the following examples which are provided for further understanding and not to limit the scope of the invention.

EXAMPLE 1 Preparation of N-[2-(2-Methoxy-phenoxy)-ethyl]-acetamide A mixture of 372 g (3 Mol) Guaiacol and 255 g (3 Mol) of 2- Methyloxazoline are heated at 160°C for 20h in a three-necked flask equipped with a stirrer, condenser and thermometer. After cooling to 90°C the reaction mixture is poured into water and the solid residue obtained is collected, washed with water and dried. The yield amounts to 480 g (76%), the obtained N-[2-(2-Methoxy-phenoxy)-ethyl]-acetamide has a melting point of 57-59°C. The N-[2-(2-Methoxy-phenoxy)-ethyl]-acetamide is used for the next step without further purification.

EXAMPLE 2 Preparation of 2- (2-Methoxy-phenoxy)-ethylamine 209 g (1 mol) of N-[2-(2-Methoxy-phenoxy)-ethyl]-acetamide are refluxed in 400 mi HCI (5n) for 4h. The pH of the reaction mixture is adjusted to 8-9 with 30% NaOH solution and the oily layer is taken up in toluene, which is evapurated afterwards. The 2-(2-Methoxy-phenoxy) ethylamine is purified by distillation under vacuum. The yield is 125 g 2- (2-Methoxy-phenoxy)- ethylamin (74,8%), the boiling point is 110-115°C at 2Torr.

EXAMPLE 3 Preparation of N-[2-(2-Ethoxy-phenoxy)-ethyl]-acetamide A mixture of 414 g (3 Mol) of guaethol and 255 g (3 Mol) of 2- Methyloxazoline are treated in the same manner as described in Example 1. About 501 g of N-[2-(2-Ethoxy-phenoxy)-ethyl]-acetamide (72%) is obtained. The N-[2-(2-Ethoxy-phenoxy)-ethyl]-acetamide has a melting point of 77-79°C and is used for the next step without further purification.

EXAMPLE 4 Preparation of 2- (2-Ethoxy-phenoxy)-ethylamine The procedure of Example 2 is followed except that 223 g of N- [2- (2- Ethoxy-phenoxy)-ethyl]-acetamide are employed. About 126 g of 2- (2- Ethoxy-phenoxy)-ethylamine (70%) are obtained. The 2- (2-Ethoxy- phenoxy)-ethylamine has a boiling point of 94-96°C at 1 Torr.