Before Chiral Drug Intermediates Synthesis And Asymmetric Transfer Hydrogenation Studies

4-benzyloxy-3-nireo-α-bromoacetophenone(1),2-bromo-1-(2,2-dimethyl- tetrahydro-1, 3-benzodioxin)-6-ethyl ketone(2)and 5-bromoacetyl salamide(3)are intermediates of formoterol,salbutamol and labetalol,which are Phenylethanolamine Derivatives.The synthetic conditions ofcompound 1,2 and 3 were investigated,and their asymmetric transfer hydrogenation with chiral catalyst(S,S)-Ru-TsDPEN(5)were studied in the paper.Compound 1 was synthesized by using salicylic acid as starting material via a three steps process including nitrification,benzyl etherification andα-bromidation in the overall yield of 58.2%.The yield of Asymmetric transfer hydrogenation of compound 1 was 85.3%with 85.0%ee.Compound 2 was synthesized by using salicylic acid as starting material via a five steps process including chloromethylation,esterification,α-bromidation,hydrolysis and ketol reaction in the overall yield of 48.0%.The yield of Asymmetric transfer hydrogenation of compound 2 was 72.1%with 84.2%ee.Compound 3 was synthesized by using salicylic acid as starting material via a four steps process including esterification,ammonolysis,Friedel-Crafts acytation andα-bromidation in the overall yield of 60.1%.5-bromoacetyl salamide acetate(4)was prepared by esterification of 3.The yield of Asymmetric transfer hydrogenation of compound 4 was 62.8%with 80.8%ee.