Methyl chloroformate → Methyl 2,4-dichloro-5-phenyl-thieno[2,3-d]pyrimidine-6-carboxylate

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Reaction Conditions

Reaction Steps

A solution of diisopropylamine (0.755 mL, 5.33 mmol) in dry tetrahydrofuran (10 mL) was cooled with an acetone/cardice bath to −55° C. under a nitrogen atmosphere. Butyllithium in hexanes (2.0 mL, 4.98 mmol, 2.5 M) was added and the temperature was allowed to rise to 0° C. for 10 min. The mixture was cooled to −55° C. and a solution of 2,4-dichloro-5-phenyl-thieno[2,3-d]pyrimidine (1.00 g, 3.56 mmol) in dry tetrahydrofuran (10 mL) was added. The mixture was stirred for 1 hr, maintaining the temperature at −55° C. Methyl chloroformate (0.561 mL, 7.11 mmol) was added and the mixture was allowed to rise to room temperature. It was stirred for 4 hr. Water (20 mL) was added to quench the reaction. The layers were separated and the aqueous was extracted with ethyl acetate (2×20 mL). The combined organic layers were dried (magnesium sulfate), filtered and evaporated to give a brown solid. (1.63 g). This was purified by silica chromatography (50 g cartridge; eluent petroleum ether 40-60/ethyl acetate 0 to 10%; collection by UV trigger). Fractions corresponding to the main peak were combined and evaporated to give the target compound as a yellow solid (1.24 g). m/z [M+H]+338.9/340.9. Retention time 4.89 min (LCMS method+ve 6 min).

Provenance & Evidence