Water → HCID 86747158, compound

Participants

Reaction Steps

To a hot mixture of 60 g of 1-[(3,4-dihydro-6,7-dimethoxy-1H-2-benzopyran-1-yl)methyl]-4-phenylmethyl-piperazine in 400 ml of ethanol was added 63,4 g of (+)-di-O,O'-p-toluoyltartaric acid. The mixture was slowely cooled down and after 12 h standing at ambient temperature, the precipitate was filtered, washed with ethanol, and recrystallized from 300 ml of ethanol to give 54,4 g of enantiomeric pure salt. The base was freed, and from 24 g of free base, 14,4 g of (+)-1 -[(3,4-dihydro-6,7-dimethoxy-1H-2-benzopyran-1-yl)-methyl]-piperazine having an enantiomeric purity >98% were obtained after hydrogenation with 5% Pd on charcoal, as described in Example 6c. 14,2 g Of (+)-1-[(3,4-dihydro-6,7-dimethoxy-1H-2-benzopyran-1-yl)methyl]-piperazine were reacted with 13,6 g of 1,1-bis(4-fluorophenyl)-4-chlorobutane and 8 g of potassium carbonate in 100 ml of dimethyl formamide for 2 h. Water was added to the mixture and after workup, the dimaleate was prepared as previously described to obtain 11,4 g of (+)-1-[4,4-bis(4-fluorophenyl)-butyl-4-[(3,4-dihydro-6,7-dimethoxy-1H-2-benzopyran-1-yl)methyl]piperazine (Z)-2-butenedioate (1:2) salt. mp 200° C. The free base has an optical rotation of [α]D20 =+38,5° (c=1, methanol).

Provenance & Evidence