Organic Chemistry of Drug Synthesis. Volume 7

A rather more complex antifungal compound incorporates in its struc-
ture both a triazole and a triazolone ring. The lengthy sequence begins
with displacement of chlorine in 171 by acetate. Reaction of the
product with the ylide from methyl triphenylphosphonium bromide
affords the methylene derivative ( 173 ). The acetate group is next saponified
to give the free alcohol. The double bond is then oxidized in the presence
ofL-ethyl tartrate to afford epoxide 174 as a single enantiomer. The first
heterocyclic ring is now introduced by opening of the oxirane with
1,3,4-triazole proper to afford 175. Reaction with methenesulfonyl chlor-
ide gives the corresponding mesylate ( 176 ). Treatment with base leads to
formation of an alkoxide on the teriary carbinol; internal displacement
forms a new oxirane. This ring is then opened by the anion from diethyl-
malonate. The alkoxide that is formed as the initial product displaces the
ethoxide group on one of the esters to form a lactone ( 178 ). Reduction
with borohydride takes both carbonyl groups to alcohols affording the
diol ( 179 ). This last intermediate ( 179 ) is again treated with toluene-
sulfonyl chloride to afford the bis(tosylate). Treatment with base leads to
formation of an alkoxide from the still free tertiary alcohol. This compound
undergoes internal displacement of one of the tosylate groups to form a
THF ring ( 180 ). The remaining tosylate function serves as a leaving

O Cl

F

F

171

NaOCOCH 3

O OCCH

3

F

F

172

1. (C 6 H 5 0) 3 P=CH 2


2. NaOH

H 2 C OH

F

F

173

O OH

F

F

174

N

N NH

OH

F

F

175

OH

N

N

N

CH 3 SO 2 Cl

OSO 2 CH 3

F

F

176

OH

N

N

N

F Base

F

177

O

N

N

N

CO 2 C 2 H 5

CO 2 C 2 H 5

F NaOH

F

178

N

N

N

O

O

CO 2 C 2 H 5

NaBH 4

F

F

N

N

N

OH OH

OH

179

1. TsSO 2 Cl


2. NaH

F

F

N

N

N

180

+ HO N N NO^2

181a

O OTs

Ti(OiPr) 3

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