DL-4-CHLOROPHENYLALANINOL synthesis

Yield:35373-63-8 40.8 %

Reaction Conditions:

with lithium aluminium tetrahydride in tetrahydrofuran at 0 - 70;

Steps:

Preparation of ((cis)-7-chloro-1-(3-chloro-5-fluorophenyl)-1,2,3,4-tetrahydroisoquinolin-3-yl)methanol (30):

Step 1 procedure was done in parallel 4X: To a suspension of lithium aluminium hydride (14.26 g, 375.69 mmol, 1.5 eq) in THF (1500 mL) was added 2-amino-3-(4-chlorophenyl)propanoic acid (50.0 g, 250.46 mmol, 1 eq) at 0°C and the mixture was brought to 20°C and stirred for 1 h and then warmed to 70°C for 10 h. LCMS showed that the desired mass was formed and the reaction mixture was cooled to 0°C and quenched by sequential addition of water (15 mL), 15% NaOH (15 mL), and water (45 mL). The mixture was filtered, the filter cake was washed with dichloromethane/tetrahydrofuran = 1/1 (800 mL, 3X), and the filtrate was concentrated. The crude residue dissolved in 4N HCl/EtOAc (300 mL) and stirred for 10 min. The mixture was filtered and concentrated to give 2-amino-3-(4-chlorophenyl)propan-1-ol as an off-white solid (92.0 g, 408.41 mmol, 40.8% yield, 98.6% purity, HCl). ESI-MS m/z = 186.1 (M+H)+

References:

Sabat;Raveglia;Aldegheri;Barilli;Bianchi;Brault;Brodbeck;Feriani;Lingard;Miura;Myers;Piccoli;Tassini;Tyhonas;Ton-Nu;Wang;Virginio [Bioorganic and Medicinal Chemistry,2022,vol. 76,art. no. 117084] Location in patent:supporting information