(R)-Arbutamin was produced as follows: 89.3 mg of (-)-1-di(tbutyldimethylsiloxy)
phenyl)-2-aminoethanol, 50.0 mg of 4-(4-
methoxymethoxyphenyl)butanoic acid, diethylphosphorylcyanide, and
triethylamine were dissolved in N,N-dimethylformamide at 0°C, reacted at
room temperature, so as to obtain 108.6 mg (in a yield of 82%) of amide
compound. The amide compound obtained was reduced lithium aluminium
hydride in an ether solvent at reflux temperature, so as to quantitative obtain
amine. And 55.6 mg of (R)-arbutamin which is intended compound was
obtained by deprotecting the hydroxyl-protecting group of amine in a
methanol-THF solvent at room temperature using hydrochloric acid.
[α]D
25 = -17 (c 1.15, EtOH).
(-)-1-(Dibutyldimethylsiloxy)phenyl)-2-aminoethanol was obtained by a
hydrogenization of (R)-1-(3,4-di(t-butyldimethylsiloxyphenyl)-2-nitroethanol on 10% Pd/C.
The last compound was prepared as follows: the hydroxyl groups of 3,4-
dihydroxy-benzaldehyde was protected using t-butyldimethylsilylchloride (1).
100 mg (0.26 mmol) of 3,4-di(t-butyl-methylsiloxy)benzaldehyde was
dissolved in 1 ml tetrahydrofurane under atmosphere of argon at -40°C, and
0.30 ml of metal complex from (S)-6,6'-bis(triethylsilylethynyl)-1,1-dihydroxy-
2,2'-binaphtalene (2) mixed with a solution of n-butyllitium in hexane.After
stirring for 30 minutes, 79.4 mg (1.3 mmol) of nitromethane was added
dropwise to the mixture. After 67 hour reaction time, 2 ml of 1 N aqueous
solution of hydrochloric acid added to stop the reaction. Product was extracted
with 50 ml ethyl acetate, dehydrated with anhydrous sodium sulfate and
concentrated within evaporator followed by silica gel chromatography (nhexane/
acetone = 10/1), after which (R)-1-(3,4-di(t-butyldimethylsiloxy)
phenyl)-2-nitroethanol with an optical purity of 92% e.e. was obtained in a
yield of 93%.
