http://rdf.ncbi.nlm.nih.gov/pubchem/patent/WO-2007125542-A2

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filingDate 2007-04-09-04:00^^<http://www.w3.org/2001/XMLSchema#date>
inventor http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_a05d8d8bbe6526601c02b6e6614514e8
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publicationDate 2007-11-08-04:00^^<http://www.w3.org/2001/XMLSchema#date>
publicationNumber WO-2007125542-A2
titleOfInvention A process for preparation of adapalene
abstract The present invention discloses a process for preparation of highly pure Adapalene, chemically designated as 6-[3-(l-adamantyl)-4-methoxy phenyl]-2-naphthoic acid (I) comprising: a) reacting 1-adamantanol with 4-bromophenol (II) in presence of sulphonic acid with or without the use of organic solvent to give 2-(l-adamantyl)-4- bromophenol (III); b) alkylating compound of formula(III) with dimethylsulphate in presence of base in organic solvent to obtain 2-(l-adamantyl)-4-bromoanisole (IV); c) C-C coupling the compound of formula (IV) with methyl-6-bromo-2- naphthoate using magnesium, purified zinc chloride and NiCl2-DPPE in THF at a temperature of 40-60°C tO obtain methyl ester of 6-[3-(l- adamantyl)-4-methoxy phenyl] -2-naphthoic acid (V); d) purifying crude methyl ester of 6-[3-(l-adamantyl)-4-methoxy phenyl]-2- naphthoic acid (V) using a mixture of organic solvent to obtain pure compound (V); e) hydrolyzing the compound (V) with a solution of alkali in organic solvent to obtain metal salt of 6-[3-(l-adamantyl)-4-methoxy phenyl] -2-naphthoic acid (VI); f) acidifying metal salt of adapalene (VI) using organic or inorganic acid to obtain crude adapalene (I) and g) recrystallizing the crude adapalene (I) using a mixture of organic solvents to obtain pure adapalene (I).
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priorityDate 2006-05-03-04:00^^<http://www.w3.org/2001/XMLSchema#date>
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