Organic Chemistry of Drug Synthesis. Volume 7

reagent and formation of 180. The ester grouping is next reduced to the corre-
sponding carbinol ( 181 ). Swern oxidation with oxalyl chloride then leads to
aldehyde 182. Treatment of this intermediate withO-methylhydroxylamine
leads to theO-methlyloxime. Thus the dopamine reuptake inhibitorbraso-
fensine( 183 )isobtained.^29

N

CH 3

O

HO 2 C

O

177

HCl

HO NCH^3

HO 2 C

178

1. POCl 3

N

CH 3

CH 3 O 2 C

179

2. CH 3 OH

NCH^3

CH 3 O 2 C

Cl

Cl

180

LiAlH 4

NCH^3

Cl

Cl

181

HO

Cl Cl

MgBr

NCH^3

Cl

Cl

182

(COCl) 2

O

CH 3 ONH 2

NCH^3

Cl

Cl

183

N

CH 3 O

Both the older tricyclic antidepressants and the more recent drugs
related to fluoxetine owe their efficacy to interaction with receptors
for the neurotransmitters epinephrine, serotonin, and dopamine. The

HO 2 C
184

+

Br

185

HO 2 C

186

Base

H 3 C

1. SO 2 Cl
   2. NaN 3

187

N 3

O

H 3 C

N

188

OC

LiAlH 4

CH 3 NH

189

N COCl

190

O

N LiAlH 4

191

64 MONOCYCLIC AROMATIC COMPOUNDS