The invention discloses a preparation method of
ramelteon. The preparation method comprises the following steps: 1, reacting
tetrahydrofuran,
sodium hydroxide and diethyl cyanomethylphosphonate to prepare a
ylide solution, and dropwise adding the
ylide solution into a solution of an initial
raw material 1 to prepare an intermediate 1; 2, reducing the intermediate 1 through
sodium borohydride under the action of
nickel chloride and di-tert-butyl
dicarbonate to obtain an intermediate 2; 3, performing
hydrochloric acid deprotection on the intermediate 2 in a
methanol solution to obtain an intermediate 3; 4, preparing an intermediate 4 through
chiral resolution and recrystallization; 4, the intermediate 4 is subjected to propionylation under the alkaline condition, and
ramelteon is obtained. According to the method, the intermediate 3 is resolved by using the
organic acid which is low in price and easy to obtain in the market. The resolution process is simple, convenient and safe to operate and suitable for industrial production, the prepared
ramelteon is high in yield and high in optical purity, and the market competitiveness of the ramelteon is enhanced.