Process and intermediates for the preparation of excitatory amino acid receptor antagonists

An enantioselective process for preparing a compound of formula (IIa) ##STR30## wherein R.sub.11 is CO.sub.2 R.sub.2, CON(R.sub.2).sub.2, CN, CH.sub.2 OH, or protected hydroxymethyl;

• R.sub.2 is independently hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 alkenyl, aryl, or C.sub.7 -C.sub.16 arylalkyl;
• R.sub.3 is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 alkenyl, CON(R.sub.6).sub.2, SO.sub.2 R.sub.6, COR.sub.6, CO.sub.2 R.sub.6, benzyl, or substituted benzyl having from one to two substituents independently selected from the group consisting of C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.8 cycloalkyl, NO.sub.2, halo, halo(C.sub.1 -C.sub.6)alkyl, C.sub.3 -C.sub.6 alkenyl, C.sub.3 -C.sub.8 cycloalkyl-(C.sub.1 -C.sub.3)alkyl, phenyl, C.sub.5 -C.sub.8 cycloalkenyl, C.sub.5 -C.sub.8 cycloalkenyl-(C.sub.1 -C.sub.3)alkyl, COR.sub.2, C.sub.1 -C.sub.10 alkanoyl, OR.sub.2, and C.sub.7 -C.sub.16 arylalkyl;
• R.sub.4 is hydrogen or CHO;
• X is --CH.sub.2 --, ##STR31## R.sub.6 and R.sub.7 independently are selected from the group consisting of C.sub.1 -C.sub.6 alkyl, aryl, C.sub.7 -C.sub.16 arylalkyl, and C.sub.3 -C.sub.6 alkenyl;
• Q is ##STR32## and R.sub.10 is silyl, C.sub.1 -C.sub.4 alkyl, or C.sub.1 -C.sub.10 alkanyoyl;
• or a pharmaceutically acceptable salt thereof;
• which process comprises contacting a substrate of the formula (Ia) ##STR33## wherein R.sub.1 is ##STR34## R.sub.11 is CO.sub.2 R.sub.2, CON(R.sub.2).sub.2, CN, CH.sub.2 OH, or protected hydroxymethyl;
• R.sub.2 is independently hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 alkenyl, aryl, and C.sub.7 -C.sub.16 arylalkyl;
• R.sub.3 is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 alkenyl, CON(R.sub.6).sub.2, SO.sub.2 R.sub.6, COR.sub.6, CO2R6, benzyl, or substituted benzyl having from one to two substituents independently selected from the group consisting of C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.8 cycloalkyl, NO.sub.2, halo, halo(C.sub.1 -C.sub.6)alkyl, C.sub.3 -C.sub.6 alkenyl, C.sub.3 -C.sub.8 cycloalkyl-(C.sub.1 -C.sub.3)alkyl, phenyl, C.sub.5 -C.sub.8 cycloalkenyl, C.sub.5 -C.sub.8 cycloalkenyl-(C.sub.1 -C.sub.3)alkyl, COR.sub.2, C.sub.1 -C.sub.10 alkanoyl, OR.sub.2, and C.sub.7 -C.sub.16 arylalkyl;
• or
• X is --CH.sub.2 --, ##STR35## R.sub.4 is hydrogen or CHO;
• R.sub.5 is silyl, C.sub.1 -C.sub.4 alkyl, or C.sub.1 -C.sub.10 alkanyoyl;
• and
• R.sub.6 and R.sub.7 independently are selected from the group consisting of C.sub.1 -C.sub.6 alkyl, aryl, C.sub.7 -C.sub.16 arylalkyl, and C.sub.3 -C.sub.6 alkenyl;
• or a pharmaceutically acceptable salt thereof;
• with a silyl compound and a tertiary amine in the presence of an organic solvent.