Organic Chemistry of Drug Synthesis. Volume 7

94. The cyclization to a quinolone ( 95 ) in this case is effected with sodium
    hydride. Treatment of this intermediate with the spiro diamine ( 96 ) leads to
    displacement of fluorine and formation of alkylation product 97.
    Deprotection by acid-catalyzed cleavage of thet-BOC group flowed by
    saponification yields the quinolone antibacterial agent 98.^17
    The first few reactions in the preparation of the most recent of this small
    set of quinolones involves adjustment of the substitution pattern on the
    central benzene ring. Thus carbonation of the lithio derivative from 99
    with carbon dioxide gives the corresponding acid; this acid is then

F

OCH 3

F

99

1. BuLi/CO 2
   2. CH 2 N 2 F
   OCH 3

F

100

CO 2 CH 3

BBr 3

F

OH

F

101

CO 2 CH 3

ClCH 2 F

F

FCH 2 O

F

102

CO 2 CH 3

1. NaN 3
   2. H 2


2. NaOH

NH 2

FCH 2 O

F

103

HONO CO^2 H

Br HBr

FCH 2 O

F

104

CO 2 Mg CO 2 H

CO 2 C 2 H 5

Br

FCH 2 O

F

105

CO 2 C 2 H 5

O

Br
FCH 2 O

F

CO 2 C 2 H 5

O

MeO 2 CHNMe 2

OCH 3

NH 2

Br

FCH 2 O

F

CO 2 C 2 H 5

O

NH

K 2 CO 3

Br

FCH 2 O

CO 2 C 2 H 5

O

N

(C 6 H 5 ) 3 C N

FCH 2 O

CO 2 C 2 H

O

(C N N

6 H 5 ) 3 C

HCl

FCH 2 O

CO 2 C 2 H 5

O

HN N

(^106107108)
109
111 110
B(OH) 2
converted to the methyl ester with diazomethane to yield 100. The methyl
ether is then cleaved by means of boron tribromide to yield 101. The newly
revealed phenol is then alkylated with chlorofluromethane in the presence
of base to afford the ether ( 102 ). Reaction of the ester with sodium azide
leads to nucleophilic aromatic displacement of the fluorine atom.

1. COMPOUNDS WITH ONE HETEROATOM 175