WO2010055004 Naphthylacetic acids

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Scaffold: naphtalene

Biological target:

Prostaglandin D2 receptors: CRTH2

Activity:

Antagonist and partial agonist

Steps Conditions Reactions
a Dimethyl succinate, tBuOK, tBuOH reflux, 3h Stobbe condensation
b

Ac2O, NaOAc, reflux, 6h

Naphthalene formation
c NaOMe, MeOH, 1h  
d Benzyl bromide, K2CO3, acetone, reflux, 4h OBn formation (OH protection)
e LiAlH4, THF, 60oC, 1h Ester reduction (OH formation)
f PPh3, CCl4, THF reflux, 2h Chlorination
g Pd(PPh3)2Cl2, K2CO3, CO gaz, MeOH/THF 1/2 Carbonylation
h H2, Pd/C, MeOH Hydrogenolysis (OH deprotection)
i K2CO3, DMF, 100oC, overnight SNAr
j 5N LiOH, THF overnight Saponification

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