1-(Chloromethoxy)-2-methoxyethane → 3,7-Dimethoxy-4-(2-methoxy-ethoxymethoxymethyl)-10-methyl-phenothiazine

Participants

Reaction Steps

A solution of 1.90 g (6.32 mmol) of 3,7-dimethoxy-10-methyl-phenothiazine-4-carbaldehyde in 30 ml of tetrahydrofuran was reduced with 7.6 ml of lithium borohydride solution (1M in tetrahydrofuran) analogously to that described in Example 4.1.1.da. The resulting 3,7-dimethoxy-10-methyl-phenothiazine-4-methanol was dissolved in 20 ml of tetrahydrofuran, whereupon 4.36 ml of n-butyllithium solution (1.6M in hexane) were added at -78°. The reaction mixture was brought slowly to 0°, then treated with 1.02 g (8.19 mmol) of 2-methoxy-ethoxymethyl chloride, stirred at room temperature for 2 hours and finally poured into ice-water/saturated sodium hydrogen carbonate solution. After three-fold extraction with diethyl ether the combined organic phases were washed with sodium chloride solution, dried over magnesium sulphate and evaporated. The residue was chromatographed on silica gel with diethyl ether/hexane (3:2), whereupon 2.09 g (84.6%) of 3,7-dimethoxy-4-(2-methoxy-ethoxymethoxymethyl)-10-methyl-phenothiazine were obtained as a colourless oil.

Provenance & Evidence