Sodium Chloride → Potassium Hydroxide

Participants

Reaction Conditions

Reaction Steps

A mixture of (1RS,2RS)-1,2,3,4-tetrahydro-1-(4-mesyloxybutyl)-6-methoxy-2-p-methoxyphenyl-2-methylnaphthalene (Example 1, 1.73 g.), potassium cyanide (0.4 g.) and dimethylsulphoxide (13 ml.) was stirred for 5 hours at 90° C. under an atmosphere of argon and then poured into saturated aqueous sodium chloride solution, and the mixture was extracted with ethyl acetate. The extract was dried and evaporated to dryness and a solution of the 5-[(1RS,2RS)-6-methoxy-2-p-methoxyphenyl-2-methyl-1,2,3,4-tetrahydronaphth-1-yl]valeronitrile thus obtained as residue (2.5 g.) and powdered potassium hydroxide (2.5 g.) in a mixture of ethane-1,2-diol (25 ml.) and water (2.5 ml.) was heated at 180° C. for 31/2 hours and then added to a mixture of ice and water. The mixture was washed with diethyl ether and the aqueous phase was acidified with aqueous 3N-hydrochloric acid and extracted with diethyl ether. The extract was dried and evaporated to dryness and a mixture of the 5-[(1RS,2RS)-6-methoxy-2-p-methoxyphenyl-2-methyl-1,2,3,4-tetrahydronaphth-1-yl]valeric acid thus obtained as residue (0.457 g.), oxalyl chloride (0.15 ml.), dimethyl formamide (1.01 ml.) and methylene chloride (20 ml.) was stirred at laboratory temperature for 2 hours and then evaporated to dryness. A solution of the residue thus obtained in methylene chloride (10 ml.) was added to a stirred solution of 3-hexylthiopropionohydrazide (0.242 g.) and triethylamine (0.15 ml.) in methylene chloride (15 ml.) and the mixture was kept at laboratory temperature for 1 hour. The reaction mixture was washed with water, dried and evaporated to dryness and the residue was purified by chromatography on a silica gel column using a 1:1 v/v mixture of toluene and ethyl acetate as eluent. There was thus obtained as an oil N1 -{b 5-[(1RS,2RS)-6-methoxy-2-p-methoxyphenyl-2-methyl-1,2,3,4-tetrahydronaphth-1-yl]valeryl}-N2 -(3-hexylthiopropionyl)hydrazine.

Provenance & Evidence