2-Chloromethyl 2-(trimethylsilyl)ethyl ether → 2,4-Dichloro-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine

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Reaction Conditions

Reaction Steps

In a 1000 mL flask, LiHMDS (140 mL, 140 mmol) was diluted in dry THF (100 mL) and cooled to −78° C. The 2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidine (25.0 g, 133 mmol) was suspended in THF (200 mL) using gentle warming and sonication. This suspension was added dropwise to the base solution over 30 min. 50 mL more THF was used to dissolve any residue and this suspension was also added dropwise. After complete addition, the mixture was allowed to stir at −78° C. for 30 min. SEM-Cl (25 mL, 140 mmol) was added dropwise to the mixture and stirring was continued at −78° C. for 30 min. Then, the ice bath was allowed to slowly warm to rt overnight. The reaction was quenched by the addition of cold water (150 mL). EtOAc (200 mL) was added and the layers separated. The resulting aqueous layer was then extracted with EtOAc (two×200 mL). The combined organics were washed with brine (two times) and dried over MgSO4, filtered and concentrated. The orange oil was purified via gravity “plug” chromatography eluting with 80% heptanes/20% DCM eluant to afford the title compound (33.4 g, 79% yield) as an orange oil which solidified upon standing. 1H NMR (400 MHz, chloroform-D) δ ppm-0.03 (s, 9H), 0.85-0.99 (m, 2H), 3.50-3.59 (m, 2H), 5.61 (s, 2H), 6.67 (d, J=3.53 Hz, 5H), 7.38 (d, J=3.78 Hz, 1H). m/z (APCI+) for C12H17Cl2N3OSi 318.00/320.05 (M+H)+ for Cl isotopes.

Provenance & Evidence