oxirane to form the dioxin ring ( 102 ). Reaction of this last compound with
carbon tetrabromide in the presence of triphenylphosphine replaces
the exocyclic hydroxyl group by bromine ( 103 ). Oxidation with per-
manganate next cleaves the double bond in the pendant allyl group to
afford the carboxylic acid ( 104 ). Catalytic hydrogenation of this intermedi-
ate serves to reduce the nitro group to the corresponding amine. This
product, which is not isolated, cyclizes to afford an amide an thus an
indolone ring 105. Displacement of bromine on the short side-chain by
benzylamine completes the synthesis of 106.^14
Many different strategies have been investigated to develop agents that
will avoid injury to the nervous system that accompanies stroke.
The recently developed agentflindokalner( 112 ), is designed to open the
so-called “maxi” potassium channels that enhance an endogenous neuro-
protective mechanism. The first step in an enantioseletcive preparation of
this compound comprises chlorination of the homosalicylate ( 107 )by
means of sulfuryl chloride. Fischer esterification in methanol affords the
CO 2 H
OCH 3107- SO 2 Cl 2
- CH 3 OH
CO 2 CH 3
OCH 3108Cl
KHDMSF 3 C NO 2FF 3 C NO 2
CO 2 CH 3
OCH 3Cl_[F+]F 3 C NO 2
CO 2 CH 3
OCH 3110ClF(^2) Separate
- Na 2 S 2 O 4
- NaOH
F 3 C NH 2
CO 2 H
OCH 3111ClFHNFOF 3 CCl112109methyl ester ( 108 ). Treatment with potassium hexamethylsisilazide leads
to formation of the benzylic anion. Reaction of this anion with the nitro
compound leads to nucleophilic aromatic displacement of the ring fluorine
atom by the benzylic anion and formation of intermediate 109. The
presence of the two electron-withdrawing groups in the nitro compound
- COMPOUNDS WITH ONE HETEROATOM 151