Organic Chemistry of Drug Synthesis. Volume 7

both reduce the double bond and to remove the benzyl protecting group
( 4 ). Reaction of 4 with hydrogen bromide then cleaves the methyl ether
on benzene to afford the free phenol and 5.^1

CH 3 O

1

O

+

N

O=HC N TiCl4

CH 3 O

N

N

3

H 2

CH 3 O

N

NH

4

HO HBr

N

NH

5

2

The antidepressant compoundlubazodone( 8 ) illustrates the breadth of
the structural requirements for serotonin selective reuptake inhibitors; the
structure of this agent departs markedly from that of fluoxetine, the first
drug in this class. The compound at hand also exemplifies the current
trend for preparing drugs in chiral form. Thus reaction of the indanol ( 6 )
with the mesylate from chiral glycidic oxide in the presence of base
leads to the epoxypropyl ether ( 7 ) with retention of chirality. Treatment
intermediate 7 with aminoethylsulfonic acid closes the morpholine ring.
Product 8 consists of pure (S) enantiomer.^2

OH

F

6

O OSO 2 CH 3

F

7

O O

H 2 N OSO^3 H

F

8

O

NH

O

Alzheimer’s disease, as noted earlier, is associated with decreased levels
of acetyl choline in the brain. Most of the drugs that have been introduced
to date for treating this disease thus comprise anticholinergic agents
intended to raise the deficient levels by inhibiting loss of existing acetyl-
choline. A compound-based on an indene perhaps surprisingly, shows

70 CARBOCYCLIC COMPOUNDS FUSED TO A BENZENE RING