Synthesis of D- and L-1-(4-Hydroxyphenyl)-2-isopropylaminoethanol

Synthesis of Chiral 1,2-Amino Alcohol-Containing Compounds Utilizing Ruthenium-Catalyzed Asymmetric Transfer Hydrogenation of Unprotected α-Ketoamines

“…24 By using this transfer hydrogenation methodology, octopamine 2e was successfully obtained in >99.9:0.1 er and 94% yield. Octopamine was also applied as a reductive amination partner in the manufacture of deterenol (2f), 25 while our method provided compound 2f in 90% yield with >99.9:0.1 er under transfer hydrogenation conditions. (R)-Denopamine, a β-receptor agonist used to treat congestive heart failure, was also synthesized in >99.9:0.1 er and 91% isolated yield with 0.2 mol % of catalyst 3l.…”

“…ethan-1one Hydrogen Chloride, 1f. 25 A 25 mL single-neck RBF equipped with a stirrer, internal thermometer, and N 2 line was charged with 1-(4hydroxyphenyl)-2-(isopropylamino)ethan-1-one (0.3 g, 4.8 mmol) and MeOH (12 V). The reaction mixture was treated with the dropwise addition of 12 M HCl (0.260 mL, 2.0 equiv) in H 2 O (3 V) at rt over a period of 5 min.…”

“…Synthesis of (R)-4-(1-Hydroxy-2-(isopropylamino)ethyl)phenol, 2f. 25 A 10 mL reactor equipped with a stirrer and N 2 line was charged with compound 1f (150 mg, 0.66 mmol), MeOH (2 mL), 3l (0.69 mg, 0.15 mol %), and formic acid/TEA (5:2) (1 V). The reaction mixture was stirred at 62 °C.…”

“…The crude mixture was then treated with aq NH 4 OH and stirred. The resulting suspension was filtered, and product 2n was obtained as a light brown solid (220 mg, 51% yield) and the presence of additional material (not quantified) was observed in the mother liquor; er ratio: 99.6:0.4; [α] D 25 AD3, 4.6 mm × 150 mm, particle size: 3 μm, temperature: 35 °C, n-heptane with 0.1% diethylamine/isopropyl alcohol with 0.1% of diethylamine = 30/70, v/v, flow rate 1.0 mL/min, 230 nm), t R = 2.9 min (major), 3.2 min (minor).…”