Process

摘要

A process for the preparation of a compound of formula (2) or (4): the process comprising reacting a compound of Formula (1) or (3) respectively with an alkylating agent R4-X in a nitrile-containing aprotic solvent in the presence of a base, wherein the process is carried out at a temeprature greater than 60°C, and the reaction mixture comprising the compound of Formula (1) or (3), the base and the aprotic solvent are heated to the temperature above 60°C prior to addition of the alkylating agent; wherein X is a halo group; R1 and R20 are H; and R2, R3, R4, R20, R21 and Y are as defined herein; and dashed bonds indicate optionally single or double bonds. The base is preferably an inorganic base, particularly a metal carbonate or bicarbonate base. The nitrile-containing solvent is preferably acetonitrile, propionitrile or butyronitrile. R4 is preferably methylcyclopropyl, methylcyclobutyl or allyl. The process is prepferably conducted in the presence of an alkali metal iodide when X is either Cl or Br. The alkylating agent is preferably added a consistent rate.