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

Temperature

2.5 °C

A solution of (5R)-3-(3-fluoro-4-iodo-phenyl)-5-hydroxymethyl-oxazolidin-2-one (1019, 25.2 g, 74.8 mmol) in methylene chloride (CH2Cl2, 150 mL) was treated with triethylamine (TEA, 15.15 g, 20.9 mL, 150 mmol, 2.0 equiv) at 25° C., and the resulting mixture was cooled down to 0-5° C. before methanesulfonyl chloride (MsCl, 10.28 g, 6.95 mL, 89.7 mmol, 1.2 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 (100 mL) and CH2Cl2 (100 mL). The two layers were separated, and the aqueous layer was extracted with CH2Cl2 (100 mL). The combined organic extracts were washed with H2O (2×100 mL) and saturated NaCl aqueous solution (100 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-iodo-phenyl)-2-oxo-oxazolidin-5-ylmethyl ester (1020, 30.71 g, 31.04 g theoretical, 98.9%) as off-white powders, which was found to be essentially pure and was directly used in the subsequent reactions without further purifications. For 1020: C11H11FINO5S, LCMS (EI) m/e 416 (M++H).

1. additionwas dropwise introduced into the reaction mixture at 0-5° C. under N2
2. customThe resulting reaction mixture
3. customthe reaction mixture was quenched with H2O (100 mL) and CH2Cl2 (100 mL)
4. customThe two layers were separated
5. extractionthe aqueous layer was extracted with CH2Cl2 (100 mL)
6. washThe combined organic extracts were washed with H2O (2×100 mL) and saturated NaCl aqueous solution (100 mL)
7. dry with materialdried over MgSO4
8. concentrationconcentrated in vacuo
9. customThe residue was further dried in vacuo

ORD record

ord-3d2249f4b1284fd4a9936864f0d00126

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08399660B2