Production of substituted indene for use e.g. as pharmaceutical intermediate, involves reaction of a 1,2-bis-halomethylbenzene as a bis-organometallic derivative with a carboxylate ester followed by dehydration of indanol

摘要

Substituted indenes (I) are obtained from 1,2-bis-halomethyl-benzenes (II) by conversion to a bis-organometallic derivative (III), reaction with a compound containing a nucleophilic leaving group attached to a carbonyl group, and dehydration of the resulting indanol. Production of substituted indenes of formula (I) and their double-bond isomers (Ia) involves conversion of 1,2-bis-halomethyl-benzenes of formula (II) into the corresponding bis-organometallic compound of formula (III), reaction with a compound of formula R1-CO-Y (IV) to give the indanol of formula (V) and elimination of water from (V). R1 = 1-40C hydrocarbyl; R2 = 6-40C aryl (optionally substituted with hydrocarbyl groups containing no hydrogens alpha to aromatic residues or vinylic groups); R3-R5 = H or 1-40C hydrocarbyl with no alpha-hydrogens as defined above, or R2 plus R3 may form a ring system with no alpha-hydrogens as defined above, or R2 may form a ring system with R3; X = halo; M = lithium, sodium, potassium or magnesium-monohalide, or two M may be Mg; and Y = a nucleophilic leaving group. An Independent claim is also included for compounds of formula (II) as new.