Preparation of Alkyl-Substituted Indoles in the Benzene Portion. Part 7. Synthesis of (±)- and (S)-(-)-Pindolol

抄録

A new, short-step synthesis of a β-adrenergic blocking agent, pindolol, 1-(4-indolyloxy)-3-(2-propylamino)-2-propanol, is described. The acid-catalyzed indole cyclization reaction of 4-[1-(4-methylphenyl)sulfonyl-3-phrroly]-4-oxobutanal (14) in the presence of (±)-3-chloro-1, 2-propanediol (12) and (R)-1-O-[(4-methylphenyl)sulfonyl]glycerol (24) afforded (±)-1-chloro-3-[1-(4-methylphenyl)sulfonyl-4-indolyloxy]-2-propanol (15) and (R)-(-)-3-[1-(4-methyl-phenyl)sulfonyl-4-indolyloxy]-1-[(4-methylphenyl)sulfonyloxy]-2-propanol (25). Reaction of these with isoproplamine and removal of the protecting group at the indole nitrogen gave (±)- and (S)-(-)-pindolol (3 and 4), thus constituting an efficient three-step synthesis of 3 and 4 from the readily available aldehyde (14).