Approaches to p-hydroxyphenoxymethylquinolines which avoid intermediate chloromethylquinolines for the synthesis of the LTD4 antagonist, RG 12525

Article abstract of DOI:10.1016/S0040-4039(96)02361-1

As part of an effort to develop an industrial synthesis of the LTD₄ antagonist RG 12525 (1), several approaches to the intermediate (2-quinolinylmethoxy)phenol 3 were investigated that avoided the generation of the lachrymatory sensitizer α-chloro-2-methylquinoline 2. Utilization of a cyclic sulfate in place of α,α'dichloro-o-xylene 4 showed promise as a selective dialkylating agent in the conversion of 3 to RO 12525 (1).