methyl 2-(4-bromophenoxy)acetate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (2S,4R)-2-(4-{Acetyl-[1-(4-methoxy-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-amino}-phenyl)-2-methyl-propionic acid was prepared via saponification of 2-(4-{acetyl-[1-(4-methoxy-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]amino}-phenyl)-2-methyl-propionic acid methyl ester, as described in the synthesis of (2S,4R)-(4-{acetyl-[1-(4-methoxybenzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-amino}-phenoxy)-acetic acid. The methyl ester was prepared following general procedure D, substituting 2-(4-bromo-phenyl)-2-methyl-propionic acid for methyl-2-(4-bromophenoxy)-acetate.

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (2S,4R)-(4-Amino-2-methyl-3,4-dihydro-2H-quinolin-1-yl)-(4-methoxyphenyl)-methanone (100 mg, 0.34 mmol), methyl-2-(4-bromophenoxy)-acetate (91 mg, 0.37 mmol), Pd2(dba)3 (17 mg, 0.02 mmol), 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (8 mg, 0.00002 mol) and cesium carbonate (0.163 g, 0.0005 mol) were taken in a round bottom flask which was then flushed with nitrogen gas through a rubber septum. Toluene (2 mL) was injected into the flask through the rubber septum and the reaction mixture was stirred at 100° C. for 24 h. After cooling to room temperature the reaction mixture was filtered through Celite® and evaporated to give the crude product (0.236 g). This crude product was purified by silica gel chromatography eluting with 100% hexanes to 50/50 hexanes/ethyl acetate gradient give the title compound (37 mg, 24%). which was then flushed with nitrogen gas through a rubber septum After cooling to room temperature the reaction mixture was filtered through Celite® evaporated to give the crude product (0.236 g) This crude product was purified by silica gel chromatography eluting with 100% hexanes to 50/50 hexanes/ethyl acetate