Novel Stereoselective Syntheses of the Fused Benzazepine Dopamine D₁ Antagonist (6aS,13bR)-11-Chloro-6,6a,7,8,9,13b-hexahydro-7-methyl- 5H-benzo[d]naphth[2,1-b]azepin-12-ol (Sch 39166):  2. l-Homophenylalanine-Based Syntheses

Two enantioselective syntheses of the fused benzazepine dopamine D1 antagonist (6aS,13bR)-11-chloro-6,6a,7,8,9,13b-hexahydro-7-methyl-5H-benzo[d]naphth[2,1-b]azepin-12-ol (1) are described in which the starting material is (+)-l-homophenylalanine (6). In the first approach, methyl (2S)-(1,2,3,4-tetrahydro-1-oxo-2-naphthalenyl)carbamate (5) is prepared by intramolecular Friedel−Crafts cyclization of N-carbomethoxy (+)-l-homophenylalanine (9). Subsequent alkylation of 5 with (4-chloro-3-methoxyphenyl)magnesium bromide, deoxygenation with Et3SiH, reduction, alkylation, and epimerization yields (+)-trans-(1R,2S)-1-(4-chloro-3-methoxyphenyl)-N-(2,2-dimethoxyethyl)-1,2,3,4-tetrahydro-N-methyl-2-naphthalenamine (2), a key intermediate in the previously described route to 1 (Draper, R. W.; Hou, D.; Iyer, R.; Lee, G. M.; Liang, J. T.; Mas, J. L.; Tormos, W.; Vater, E. J.; Gunter, F.; Mergelsberg, I.; Scherer, D. Org. Process Res. Dev. 1998, 2, XXXXX). A complementary route to 2 is also described in which arylation...