The Synthesis And Characterization Of (R)-DAIPEN

(R)-DAIPEN was prepared starting from D-valine. The crucial steps in the synthesis were found as follows: firstly, D-valine/dichloride sulfoxide=1:1.2(mole ratio), reaction temperature: room temperature, reaction time 1h;and then refluxing for 3h. The solvent was removed in a rotary evaporator, and the solid can be used to nextreaction without recrystallization; in the second step, (R)-methyl-2-amino-3-methyl -butanoate hydrochloride/p-methoxypenyl magnesium bromide=1:6, reaction temperature: room temperature, reaction time:24h, after removing the solvent, theresulting slurry was crystallized from ether and recrystallized from ethyl acetate; in the third step, (R)-2-amino 1,1-bis(4-methoxyphenyl)-3-methylbutan-1-ol /CbzCl/ NaOH=1:3:4, reaction at room temperature for 4h. Recrystallization of samples from ester:ethanol=20:1 gives the pour solid; in the fourth step, (R)-benzyl 1-hydroxy-1,1-bis(4-methoxyphenyl)-3-methylbutan-2-ylcarbamate/NaN₃/TFA=1:2:5, reaction at 0℃for 4h and then at room temperature for 12h, after removing the solvent, the resulting slurry can be used to next reaction without recrystallization; in the last step, hydrogenation at room temperature for 24h(pressure,50psi,10%Pd/C). After hydrogenation the desired diamine could isolated by recrystallization from diethyl ether. Overall yield: 28.32%.