The Grignard reaction of cis-3-phenyl-4-p-acetoxyphenyl-7-methoxy-3,4-dihydrocoumarin (I) with methylmagnesium iodide (A) in THF gives erythro-2-methyl-3-phenyl4-(p-hydroxyphenyl)-4-(2-hydroxy-4-methoxyphenyl)-4-(2-hydroxy-4-methoxyphenyl)butan-2-ol (II), which is cyclized with PPA at 75-80 C yielding cis-2,2-dimethyl-3phenyl-4-p-hydroxyphenyl-7-methoxychroman (III). This compound can also be obtained by hydrogenation of 2,2-dimethyl-4-p-hydroxyphenyl-3-phenyl-7-methoxychromene (IV) with H2 over Pd/C in THF. The condensation of (III) with N-(2-chloroethyl)pyrrolidine (B) by means of K2CO3 in refluxing acetone affords 3,4-cis-2,2-dimethyl-3-phenyl-4-[p-(beta-pyrrolidinoethoxy)phenyl]-7-methoxychromane (V), which is finally isomerized with n-butyllithium in DMSO.
The Grignard reaction of trans-3-phenyl-4-p-acetoxyphenyl-7-methoxy-3,4-dihydrocoumarin (VI) with methylmagnesium iodide (A) in THF gives a mixture of cis-2,2-dimethyl-3-phenyl-4-p-hydroxy-phenyl-7-methoxychromane (VII) and threo-2-methyl-3-phenyl-4-(p-hydroxyphenyl)-4-(2-hydroxy-4-methoxyphenyl)butan-2-ol (VIII), which can be cyclized to (VII) with PPA at 75-80 C. Finally, (VII) is condensed with N-(2-chloroethyl)-pyrrolidine (B) by means of K2CO3 in refluxing acetone.