Prepn. of antihypertensive (R,R)-labetalol - by use of stereospecific intermediates obtd. by resolution

摘要

Prepn. of (-)-5-((R)-1-hydroxy 2-((R)-1-methyl-3-phenylpropyl) aminoethyl)salicylamide (I) or its acid-addn. salts includes the redn. of the glycyl carbonyl function of a 2-(opt. protected OH)-5-(N-protected-N-((R) 1-methyl-3-phenylpropyl) glycyl)benzamide (II). The N-protecting gp. is a (R)-ArCHY-qp. (Ar is aryl esp. aryl having a single benzene ring; and Y is 1-6C alkyl) esp. (R)-alpha-methylbenzyl go. Intermediates of formula (IIa) are new. (Ar is aryl: Y is 1-6C alkyl; Z is H or 3-(H2NOC)-4-(P'O)C6H3X-CH2; p' is a protecting gp. removable by hydrogenolysis; and X is CO or (R1S)CH(OH)). (I) is one of the 4 optically active stereoisomers found in the antihypertensive agent labetalol described in US4012444, and (I) and its prepn. are described in EP--9702. By using the stereospecific intermediates (II), which can be obtd. by resolution through salt formation, without the need for chromatographic sepns. etc.