Trifluoroacetic acid → HCID 60104786, compound

Participants

Reaction Steps

Trifluoroacetic acid (5.0 mL, 64.9 mmol) is added to a solution of 2-(S)-(1-o-tolyl-3,4-dihydro-1H-isoquinolin-2-yl)-propionic acid tert-butyl ester (0.27 g, 0.768 mmol) in dichloromethane (5.0 mL). The reaction mixture is stirred at room temperature for 4 hours. All solvent is removed in vacuo, ethyl ether (50 mL) and saturated sodium bicarbonate (100 mL) are added and the organic layer is removed. The aqueous layer is acidified to pH 2.0 using 1M HCl and the crude product extracted into dichloromethane (100 mL), washed with water (2×50 mL) and brine (1×100 mL), and dried over magnesium sulfate. Filtration and concentration are followed by flash chromatography on SiO2 using 20:1 dichloromethane:methanol and afford 100 mg 2-(S)-[1-(R)-o-tolyl-3,4-dihydro-1H-isoquinolin-2-yl]-propionic acid (Rf of 0.6) and 70 mg 2-(S)-[1-(S)-o-tolyl-3,4-dihydro-1H-isoquinolin-2-yl]-propionic acid (Rf of 0.3) both as white foams. 2-(S)-[1-(R)-o-tolyl-3,4-dihydro-1H-isoquinolin-2-yl]-propionic acid, 2-(R)-[1-(S)-o-tolyl-3,4-dihydro-1H-isoquinolin-2-yl]-propionic acid and 2-(R)-[1-(R)-o-tolyl-3,4-dihydro-1H-isoquinolin-2-yl]-propionic acid are prepared in similar fashion. D. N-(2-fluoro-benzyl)-N-indan-2-yl-2-(S)-[1-(S)-o-tolyl-3,4-dihydro-1H-isoquinolin-2-yl]-propionamide (Compound 9)

Provenance & Evidence