7-Methoxy-1,2,3,4-tetrahydronaphthalen-1-one → 7-Methoxynaphthalene-1-carbonitrile

Participants

Reaction Conditions

Reaction Steps

In a highly preferred aspect of this invention illustrated in Scheme 1, there is provided a new and improved process for the large-scale production of 3-(3-fluoro-4-hydroxyphenyl)-7-hydroxy-1-naphthonitrile (1). Commercial material 3,4-dihydro-7-methoxy-1(2H)-naphthalenone (7-methoxy-1-tetralone) may be transformed into an unsaturated nitrile (3) as shown on Scheme 1. The reaction is performed in toluene solution. Upon the completion of the reaction, it is quenched by caustic solution. The reaction mixture is extracted with toluene. After washing the toluene solution, the crude unsaturated nitrile (3) is aromatized directly in this toluene solution by stirring with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) at 60° C. for 2 h. The solid is removed by filtration and the filtrate is washed with sodium hydroxide solution and brine and respectively. Most of the solvent is removed by distillation and heptane is added to precipitate the product. 7-methoxy-1-naphthonitrile (4) is isolated. The expected yield over these two steps is at least 70-75%. By performing two reactions in the same solvent, isolation of the low melting point intermediate (3) can be avoided, improving efficiency and yield.

Provenance & Evidence