PRODUCTION OF GROWTH HORMONE SECRETION PROMOTIVE AGENT

摘要

PROBLEM TO BE SOLVED: To obtain an intermediate for producing the subject medicament in high yield by mixing a specific chiral tartaric acid salt with an organic amine in an inert solvent within a specific temperature range and then adding a specific carboxylic acid compound and a coupling reagent successively to the slurry formed above so as to avoid any cryogenic filtration operation. SOLUTION: This intermediate of formula III is obtained by mixing a chiral tartaric acid salt of formula I (R1 is a 1-10C alkyl substitutable <=3 fluoro groups; R2 is phenylmethyl or the like) with an organic amine (pref. triethylamine) in an inert solvent at about -68 to -40 deg.C to form a slurry, adding a compound of formula II (R3 is a 1-5C alkyl-O-0-5C alkylphenyl, the phenyl being substitutable with <=3 fluoro groups; Prt is an amine-protective group) to the above slurry to form a reaction mixture comprising the organic amine tartaric acid salt, the free base derived from the compound of formula I and the compound of formula II, and then adding a coupling reagent (pref. propanephosphonic anhydride) to the above reaction mixture.