Method for preparing atomoxetine
AssigneeSCI Pharmtech, Inc.
InventorsBo-Fong Chen, Yan-Wei Li, Jinun-Ban Yeh, Wei-Chyun Wong
Life of this patent
Estimating the term…
Abstract
The present invention provides an efficient method for preparing atomoxetine in high yield. (R)-methylhydroxylaminopropanol compound of formula (II) in the present invention is used as an intermediate without the need for resolution processes.
Claims17
An optical active (R)-methylhydroxylaminopropanol compound of formula (II) or its acid addition salts:
- wherein R is a hydrogen atom, an alkyl group having 1 to 8 carbon atoms or an aryl group having 6 to 10 carbon atoms, and an absolute configuration of a chiral center of formula (II) is R.
A method for preparing an optical active (R)-methylhydroxylaminopropanol compound of formula (II) or its acid addition salts, comprising the steps of:
- performing a Mannich reaction of acetophenone, formaldehyde and a methylhydroxylamine of formula, HNCH3(OR), to form a substituted amino ketone of formula (I)
- and
- reducing the substituted amino ketone of formula (I) enatio selectively to form (R)-methylhydroxylaminopropanol compound of formula (II)
- wherein R is a hydrogen atom, an alkyl group having 1 to 8 carbon atoms or an aryl group having 6 to 10 carbon atoms.
A method for preparing (R)-(−)-N-methyl-3-(2-methylphenoxy)-3-phenylpropylamine, comprising the steps of:
- performing a Mannich reaction of acetophenone, formaldehyde and a methylhydroxylamine of formula, HNCH3(OR), to form a substituted amino ketone of
- reducing the substituted amino ketone of formula (I) enatio selectively to form (R)-methylhydroxylaminopropanol compound of formula (II)
- performing an N,O-cleavage reaction of the (R)-methylhydroxylaminopropanol compound of formula (II) to form (R)-N-methyl-3-hydroxy-3-phenylpropylamine of formula (III)
- and
- performing ether formation of (R)-N-methyl-3-hydroxy-3-phenylpropylamine of formula (III) with 2-fluorotoluene to provide (R)-(−)-N-methyl-3-(2-methylphenoxy)-3-phenylpropylamine,
- wherein R is a hydrogen atom, an alkyl group having 1 to 8 carbon atoms or an aryl group having 6 to 10 carbon atoms.
Dependencies are inferred from the claim text.