| 摘要 |
The present invention relates to a process for the preparation of (-)-3,4-trans-diarylchromans of formula (I), wherein R<1>, R<4> and R<5> are individually hydrogen, hydroxy, halogen, trifluoromethyl, C1-6alkyl, C1-6alkoxy or -O-(CH2)n-NR<6>R<7> wherein n is an integer in the range of 1 to 6 and R<6> and R<7> independently are C1-6alkyl or R<6> and R<7> together with the N atom is a saturated or unsaturated 5- or 6-membered heterocyclic group containing one or two heteroatom(s) which heterocyclic group is optionally substituted with C1-6alkyl; and R<2> and R<3> are individually hydrogen or C1-6alkyl; and salts thereof. The present invention provides a process which comprises reacting a (+,-)-3,4-cis-diarylchroman with a chiral acid, e.g. (-)-di-p-toluoyltartaric acid, in an inert organic solvent to obtain the chiral acid salt, e.g. (-)-di-p-toluoyltartaric acid salt, of the (-)-3,4-cis enantiomer in crystalline form, subjecting the crystalline salt to hydrolysis and rearranging the (-)-3,4-cis enantiomer to the (-)-3,4-trans enantiomer with a strong base in an inert aprotic solvent.
|
