Bromotrimethylsilane → HCID 57133618, compound

Participants

Reaction Conditions

Reaction Steps

(5S)-2-(t-Butyldimethylsilyloxy)-5-(4-fluorophenyl) tetrahydrofuran (212, 1 g, 3.4 mmol) was dissolved in 10 mL of dry methylene chloride (degassed by bubbling argon prior to use). This solution was cooled to -70° C. and, while stirring at the same temperature under dry argon, trimethylsilyl bromide (550 μL, 4.1 mmol) was added dropwise. The stirring was continued for an additional 1.5 hours to yield (5S)-2-bromo-5-(4-fluorophenyl) tetrahydrofuran which was used without isolation (see below). In a separate flask, 3-t-butyldimethylsilyloxy-but-1-yne (840 mg, 4.5 mmol) was dissolved in dry THF (10 mL). The solution was cooled to -60° C. and, while stirring at the same temperature under dry argon, n-butyllithium (1.8 mL of 2.5M solution in hexane, 4.5 mmol) was added dropwise. The stirring was continued for an additional 0.5 hours. The resulting solution was added dropwise, through a cannula to the stirred solution of the 2-bromotetrahydrofuran (made above) at -70° C. The stirring was continued at -78° C. for additional 1.5 hours. The reaction flask was then left in the freezer (-78° C.) over night (though the TLC did not show any change). The reaction mixture was poured into 2M solution of ammonium chloride (100 mL) and extracted with methylene chloride (3×75 mL). The solution was dried over sodium sulfate and the solvent removed in vacuo; The residue was purified via flash column chromatography (eluent, 10% ethyl acetate in hexane) to obtain two components. From the proton NMR analysis, the less polar one was identified as (2S,5S)-trans-2-(3-t-butyldimethylsilyloxy-but-1-ynyl)-5-(4-fluorophenyl) tetrahydrofuran (213, 765 mg, 65%). 1H-NMR (CDCl3) δ 7.29 (2H, m), 7.01 (2H, t, J=8.7 Hz), 5.09 (1H, t, J=7.1 Hz), 4.91-4.97 (2H, m), 4.55-4.62 (1H, m), 2.26-2.50 (2H, m), 2.05-2.17 (1H, m), 1.75-1.88 (1H, m), 1.38 (3H, d, J=6.6 Hz), 0.90 (9H,s), 0.12 (6H, s). The more polar component was assigned to be (2R,5S)-cis-2-(3-t-butyldimethylsilyloxy-but-1-ynyl)-5-(4-fluorophenyl) tetrahydrofuran (214, 190 mg, 16%).

Provenance & Evidence