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

HRID 2402969Notes

Reaction equation

HRID 2402969 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:13][C@H:12]([CH2:14][OH:15])[O:11][C:10]2=[O:16])[CH:5]=[CH:6][C:7]=1[I:8].C(N(CC)C(C)C)(C)C.[CH3:26][S:27](Cl)(=[O:29])=[O:28]>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:13][C@H:12]([CH2:14][O:15][S:27]([CH3:26])(=[O:29])=[O:28])[O:11][C:10]2=[O:16])[CH:5]=[CH:6][C:7]=1[I:8]

Participants

5

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 20788885Compound 3

Product 1

HCID 23624705Methanesulfonic acid (5R)-3-(3-fluoro-4-iodo-phenyl)-2-oxo-oxazolidin-5-ylmethyl esterYield 97.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
2.5 °C

Procedure

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).

Workup

  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 (60 mL) and CH2Cl2 (60 mL)
  4. customThe two layers were separated
  5. extractionthe aqueous layer was extracted with CH2Cl2 (60 mL)
  6. washThe combined organic extracts were washed with H2O (2×60 mL) and saturated NaCl aqueous solution (40 mL)
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated in vacuo
  9. customThe residue was further dried in vacuo

Sources & evidence

ORD record
ord-03bfd94e9dae449ebf0affbff57d1f29
Source dataset
uspto-grants-2014_08
Patent number
US08796465B2

Reaction notes

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