Benzene, 1-(chloromethyl)-2-fluoro- → 1,2,3,4-Tetrahydroisoquinolin-4-ol

Participants

Reaction Steps

To prepare the parent ring system 7, i.e., the spiro[benzofuran-2(3H),4'(2'H)-isoquinoline] 1 wherein R is hydrogen, a 2,3-dihydro-4(1H)isoquinoline 3 wherein R is loweralkyl or benzyl is treated with a Grignard reagent 4, prepared from a 2-fluorobenzyl chloride or 2-fluorobenzyl bromide by conventional methods, to afford the 1,2,3,4-tetrahydro-4-isoquinolinol 2, which is cyclized to the spiro[benzofuran-2(3H),4'(2'H)-isoquinoline] 5, wherein R is loweralkyl or benzyl and dealkylated or debenzylated to spiro[benzofuran-2(3H),4'(2'H)-isoquinoline] 7, via the alkoxycarbonyl or phenoxycarbonyl derivative 6 wherein R1 is loweralkyl or phenyl, respectively. (See Reaction Scheme I).

Provenance & Evidence