4-Toluenesulfonyl chloride → 4-Chloro-7-(3-methyloxetan-3-YL)-7H-pyrrolo[2,3-D]pyrimidine

Participants

Reaction Conditions

Reaction Steps

n-BuLi (6.6 mL of a 2.5 M solution in hexane, 16.5 mmol) was added to a solution of 2-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-methylpropane-1,3-diol (Preparation 217, 3.63 g, 15.0 mmol), in THF (80 mL) at −78° C. The reaction mixture was allowed to warm to −50° C. in 2 hours and TsCl (3.15 mg, 16.5 mmol) in THF (20 mL) was added to the reaction. The reaction was allowed to warm to 0° C. in 3 hours and additional n-BuLi (6.6 mL of a 2.5 M solution in hexane solution, 16.5 mmol) was slowly added to the reaction mixture. The mixture was stirred for 1 hour at 0° C. and stirred at 60° C. for 16 hours. After cooling to room temperature, the reaction was quenched by 50 mL of saturated aqueous NH4Cl solution and 100 mL of water, and the mixture was extracted with EtOAc (3×100 mL). The combined organic layers were dried over MgSO4 and concentrated in vacuo. The crude residue was purified by column chromatogranhy on silica gel (gradient of EtOAc:heptane 20:80 to 70:30) to give a solid in 55% yield, 1.87 mg.

Provenance & Evidence