Sodium hydride → (RS)-5-[2-cyano-5-(3-thienylmethoxy)phenoxy]-5-(2-methylphenyl)pentanoic acid

Participants

Reaction Conditions

Reaction Steps

To a stirred suspension of sodium hydride (0.69 g, 60% dispersion in mineral oil) in dry tetrahydrofuran (50 mL) is added a solution of sodium (RS)-5-hydroxy-5-(2-methylphenyl)pentanoate (1.23 g) in dry tetrahydrofuran (100 mL). The mixture is stirred at room temperature for 1.5 hours when 2-fluoro-4-(3-thienylmethoxy)benzonitrile (1.57 g) is added in one portion. The reaction mixture is heated at 55-60° C. for 18 hours and evaporated. The residue is dissolved in water (100 mL), the solution acidified to pH 1 with 1 N hydrochloric acid and the mixture extracted three times with ethyl acetate (100 mL). The combined extracts are washed with brine (100 mL), dried over magnesium sulphate and evaporated to give (RS)-5-[2-cyano-5-(3-thienylmethoxy)phenoxy]-5-(2-methylphenyl)pentanoic acid as a white waxy solid (0.4 g), mp.p.106-108° C. [Elemental analysis:- C,67.15; H,5.84; N,2.75; S,6.99%. Calculated for C24H23NO4S.0.5EtOAc:- C,66.66; H,4.66; N,6.48%].

Provenance & Evidence