Organic Chemistry of Drug Synthesis. Volume 7

( 6 ). The free phenol group on the newly introduced ring is then alkylated
withN,4-chloroethylpiperidine to give the basic ether ( 7 ). Reaction of 7
with methylmagnesium bromide followed by treatment with acid leads
the first-formed alcohol to dehydrate; at the same time the tetrahydropyrra-
nyl groups hydrolyze to reveal the free phenols 8. Separation on a chiral
chromatographic column then affords the (S) isomer, 9.^1

OH

HO

1

+

HO 2 C

OH

2 OH

HO

OH

O

3

DHP

OH

THPO

OTHP

O

4

CH=O

HO

[B–]

OH

THPO

OTHP

O

OH

O

THPO

OTHP

O

OH

(^65)
O
THPO
OTHP
O
O
7
N
Cl N
Cs 2 CO 3

1. CH 3 MgBr

O

HO

OH

O N

O

HO

OH

O N

2. AcOH

8 9

Chiralpak

Migraine was a condition that was refractory to treatment until the dis-
covery of the serotonin receptor blocker, such as sumatriptan. This agent
was soon followed by several other drugs that acted by the same mechan-
ism.Tidembersat( 13 ) a compound more closely related, both in structure
and mechanism of action, to antihypertensive benzopyrans that act on

164 SIX-MEMBERED HETEROCYCLES FUSED TO ONE BENZENE RING