Hydrochloric Acid → (2-fluoro-3-nitro-phenyl)-(7H-pyrrolo[2,3-d]pyrimidin-5-yl)-methanol

Participants

Reaction Conditions

Reaction Steps

To 5-iodo-7H-pyrrolo[2,3-d]pyrimidine (35, 1.911 g, 7.799 mmol) 9.75 mL of tetrahydrofuran was added, the suspension was cooled to −5° C., and o-tolylmagnesium chloride (8.19 mL, 1.00 M in tetrahydrofuran, 8.19 mmol) was added. The reaction solution was stirred and kept between −5° C. and 0° C. for 30 minutes, then isopropylmagnesium chloride (4.29 mL, 2.0 M in tetrahydrofuran, 8.58 mmol) was slowly added dropwise. The reaction mixture was stirred and kept at 0° C. for 30 minutes, then 2-fluoro-3-nitro-benzaldehyde (36, 1.58 g, 9.36 mmol) in 4 mL of tetrahydrofuran was added dropwise using a syringe. The reaction mixture was stirred at −5° C. for 30 minutes and quenched with 1 N hydrochloric acid (1 equivalent) and extracted with ethyl acetate and saturated sodium bicarbonate in water. The organic layer was dried over magnesium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material was purified by silica gel column chromatography eluting with a gradient of 60-80% ethyl acetate in hexanes (with 4% acetic acid). Appropriate fractions were combined and concentrated under vacuum to provide the desired compound (37, 699 mg). MS(ESI) [M+H+]+=289.4.

Provenance & Evidence