A process for the enantiospecific synthesis of intermediates for hexahydro-benzo¬d naphto¬2,1-b azepines

摘要

Biologically active, enantiomerically substantially pure intermediates of trans-hexahydro-benzo[d]naphtho[2,1-b] azepines are prepared. The present invention involves a process for preparing compounds of the general formula 3: <CHEM> Each R<1> is independently H or alkyl; Q is methylene, -O- or -S-; m and n are independently variable and may each have a value of 0, 1 or 2 with the provisos that the sum of m and n is not greater than 3, that m may not equal zero when Q is -O- or -S-, and that when Q is -CH2-, m and n cannot both be zero; X is hydrogen, halo, alkyl, alkylthio, alkylsulfinyl, alkylsufonyl, hydroxy, alkoxy or trifluoromethyl; Y is hydrogen, hydroxy, alkoxy, -OC(O)NR<2>R<3>, -OC(O)-R<9>, -N(R<1>)2, -NHC(O)R<1> or -OP(O)(OH)OR<1>; R<2> and R<3> are the same or different and each is hydrogen (provided that both are not hydrogen), alkyl, aralkyl, cycloalkyl, aryl, hydroxyalkyl, or alkoxyalkyl; in addition, when one of R<2> and R<3> is as defined above, the other may be -R<4>NR<5>R<6> {wherein R<4> is alkanediyl, R<5> is hydrogen or alkyl and R<6> is alkyl, or R<5> and R<6> together with the nitrogen atom form a 1-azetidinyl, 1-pyrrolidinyl, 1-piperidinyl, 1-(4-alkylpiperazinyl), 4-morpholinyl or 1-(hexahydroazepinyl) group}; in further addition, R<2> and R<3> together with the nitrogen atom may form a 1-azetidinyl, 1-pyrrolidinyl, 1-piperidinyl, 4-morpholinyl, 1-(4-alkylpiperazinyl), 1-(4-alkoxyalkylpiperazinyl), 1-(4-hydroxyalkylpiperazinyl), 1-(3-hydroxyazetidinyl), 1-(3-alkoxyazetidinyl), 1-(-hydroxypyrrolidinyl), 1-(3-alkoxypyrrolidinyl), 1-(3- or 4-hydroxypiperidinyl), 1-(3- or 4-alkoxypiperidinyl), 1-(4-oxopiperidinyl) or 1-(3-oxopyrrolidinyl) ring; in still further addition, when R<2> is hydrogen, R<3> may be -CHR<7>CO2R<8>, wherein R<7> and R<8> are the same or different and each is hydrogen, alkyl or aralkyl; R<9> is alkyl, aralkyl, aryl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, cycloalkylalkyl, alkoxycarbonylalkyl, cycloalkyl, 1-adamantyl, cycloalkoxyalkyl, alkoxy, aralkyloxy, cycloalkoxy, aryloxy or -CHR<7>NHR<8> ; and Z is X as defined above, amino, alkylamino or -NHC(O)R<1><0> {wherein R<1><0> is hydrogen, alkyl or aryl}; R<1><1> is H or alkyl; R<1><2> is alkyl; with the proviso that R<1><1> and R<1><2> are different, and K is hydrogen, alkoxy, hydroxyl, arloxy or alkyl.