Patent ID: 8324404
Filing Date: 2012-12-04
Classification: A61P,C07D

Abstract:
1. A process for the preparation of a compound of formula 8 in which R1 is 1-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmethoxy or 1-4C-alkoxy which is completely or predominantly substituted by fluorine, R2 is 1-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmethoxy or 1-4C-alkoxy which is completely or predominantly substituted by fluorine, or in which R1 and R2 together are a 1-2C-alkylenedioxy group, comprising: (a) reacting a compound of formula 12 with concentrated hydrobromic acid under strictly anhydrous conditions, (b) subjecting the resulting 1-bromo-1-(3,4-dialkoxyphenyl)ethane derivative of formula 11 to a bromo-lithium exchange reaction and then converting with acrolein to yield a 2-(3,4-dialkoxyphenyl)-1,4-pentadien-3-ol derivative of formula 10 (c) oxidizing the 2-(3,4-dialkoxyphenyl)-1,4-pentadien-3-ol derivative of formula 10 to the corresponding 2-(3,4-dialkoxyphenyl)-1,4-pentadien-3-one derivative of formula 9 (d) and converting the 2-(3,4-dialkoxyphenyl)-1,4-pentadien-3-one derivative of formula 9 to a 3-(3,4-dialkoxy-phenyl)-tetrahydro-thiopyran-4-one derivative of formula 8 via a double Michael addition with Na