Preparation of alkyl-substituted indoles in the benzene portion. Part 7. Synthesis of (±)- and (S)-(-)-pindolol

Article abstract of DOI:10.1248/cpb.40.2353

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-pyrrolyl]-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-methylphenyl)sulfonyl-4-indolyloxy]-1-[(4-methylphenyl sulfonyloxy]-2-propanol (25). Reaction of these with isopropylamine 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).