(3-Bromopropoxy)(tert-butyl)dimethylsilane → 5-[2-(tert-Butyldimethylsiloxy)propyl]-4-chloro-7H-pyrrolo[2,3-d]pyrimidine

Participants

Reaction Conditions

Reaction Steps

A suspension of compound 2.2 (10.0 g, 43.0 mmol) in THF (140.0 mL) was cooled to −78° C. under an argon atmosphere and n-BuLi (1.6M in hexanes, 67.3 mmol) was then added via syringe over 1.5 hr. The resulting suspension was stirred for the next 30 min at −78° C. then (3-bromopropoxy)-tert-butyldimethylsilane (21.4 mL, 172.0 mmol) was slowly added via syringe at −78° C. over 1 hr. The reaction mixture was allowed to slowly reach −30° C. and stirred for the next 2 h, and −30 to 10° C. for 1 h, and −10 to 0° C. for 1 hr. The reaction mixture became dark brown in color, and was kept at 4° C. overnight. The reaction was quenched by adding aqueous NH4Cl (100 mL), and diluted with CH2Cl2 (600 mL) and water (120 mL) then extracted with CH2Cl2. The combined organic layers were dried over Na2SO4, filtered and evaporated. The beige colored residue was purified by flash column chromatography using 25% EtOAc in hexanes as eluent to give the desired compound 4.1 (5.5 g) as a white solid.

Provenance & Evidence