Methanesulfonyl chloride → Methanesulfonic acid (5R)-3-(3-fluoro-4-iodo-phenyl)-2-oxo-oxazolidin-5-ylmethyl ester

Participants

Reaction Conditions

Reaction Steps

A solution of (5R)-3-(3-fluoro-4-iodophenyl)-5-hydroxymethyl-oxazolidin-2-one (1019, 11.66 g, 34.6 mmol) in methylene chloride (CH2Cl2, 80 mL) was treated with N,N-diisopropylethylamine (Hunig's base, DIEA, 8.95 g, 12.1 mL, 69.2 mmol, 2.0 equiv) at 25° C., and the resulting mixture was cooled down to 0-5° C. before methanesulfonyl chloride (MsCl, 4.36 g, 2.95 mL, 38.1 mmol, 1.1 equiv) was dropwise introduced into the reaction mixture at 0-5° C. under N2. The resulting reaction mixture was subsequently stirred at 0-5° C. for 1 h under N2. When TLC and HPLC/MS showed that the reaction was complete, the reaction mixture was quenched with H2O (60 mL) and CH2Cl2 (60 mL). The two layers were separated, and the aqueous layer was extracted with CH2Cl2 (60 mL). The combined organic extracts were washed with H2O (2×60 mL) and saturated NaCl aqueous solution (40 mL), dried over MgSO4, and concentrated in vacuo. The residue was further dried in vacuo to afford the crude, (5R)-methanesulfonic acid 3-(3-fluoro-4-iodophenyl)-2-oxo-oxazolidin-5-ylmethyl ester (1020, 14.0 g, 14.36 g theoretical, 97.5%) as off-white powders, which was found to be essentially pure and was directly used in the subsequent reactions without further purifications. For 1020: 1H NMR (300 MHz, DMSO-d6) δ 3.26 (s, 3H, OSO2CH3), 3.83 (dd, 1H, J=6.4, 9.2 Hz), 4.19 (t, 1H, J=5.4 Hz), 4.44-4.54 (m, 2H), 5.01-5.06 (m, 1H), 7.22 (dd, 1H, J=2.4, 8.7 Hz), 7.56 (dd, 1H, J=2.4, 8.7 Hz), 7.84 (dd, 1H, J=7.5, 8.7 Hz); C11H11FINO5S, LCMS (EI) m/e 416 (M++H).

Provenance & Evidence