Acetic Anhydride → (S)-N-[3-(3-Fluoro-4-iodo-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-acetamide

HRID 2190686Notes

Reaction equation

HRID 2190686 reaction equation
[NH2:1][CH2:2][C@@H:3]1[O:7][C:6](=[O:8])[N:5]([C:9]2[CH:14]=[CH:13][C:12]([I:15])=[C:11]([F:16])[CH:10]=2)[CH2:4]1.[C:17](OC(=O)C)(=[O:19])[CH3:18]>C(Cl)Cl>[F:16][C:11]1[CH:10]=[C:9]([N:5]2[CH2:4][C@H:3]([CH2:2][NH:1][C:17](=[O:19])[CH3:18])[O:7][C:6]2=[O:8])[CH:14]=[CH:13][C:12]=1[I:15]

Participants

4

Reactant 2

HCID 7918Acetic AnhydrideHCID 58721926(S)-5-(aminomethyl)-3-(3-fluoro-4-iodophenyl)oxazolidin-2-one

Product 1

HCID 11222662(S)-N-[3-(3-Fluoro-4-iodo-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-acetamideYield 96.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
2.5 °C

Procedure

A suspension of amine 107 (16.0 g, 47.6 mmol) in CH2Cl2 (150 mL) was treated with TEA (9.62 g, 13.2 mL, 95.2 mmol, 2.0 equiv) at 25° C., and the resulting reaction mixture was cooled to 0-5° C. before being treated with acetic anhydride (Ac2O, 7.29 g, 6.75 mL, 71.4 mmol, 1.5 equiv) and 4-N,N-dimethylaminopyridine (DMAP, 58 mg, 0.5 mmol, 0.01 equiv) at 0-5° C. under N2. The resulting reaction mixture was subsequently stirred at 0-5° C. for 2 h. When TLC and HPLC showed the reaction was complete, the reaction mixture was quenched with H2O (100 mL). The two layers were separated, and the aqueous layer was extracted with CH2Cl2 (2×50 mL). The combined organic extracts were washed with H2O (2×100 mL) and saturated aqueous NaCl (100 mL), dried over MgSO4, and concentrated in vacuo. The residue was further dried in vacuo to afford the desired (5S)—N-[3-(3-fluoro-4-iodo-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-acetamide 108 (17.36 g, 96.5% yield) as a white powder. This product was directly used in subsequent reactions without further purification. 1H NMR (300 MHz, DMSO-d6) δ 1.63 (s, 3H, NHCOCH3), 3.25 (t, 2H, J=5.4 Hz), 3.56 (dd, 1H, J=6.4, 9.2 Hz), 3.95 (t, 1H, J=9.1 Hz), 4.58 (m, 1H), 5.16 (t, 1H, J=5.7 Hz, OH), 7.02 (dd, 1H, J=2.4, 8.2 Hz), 7.38 (dd, 1H, J=2.4, 10.8 Hz), 7.66 (t, 1H, J=7.5, 8.4 Hz), 8.08 (t, 1H, J=5.8 Hz, NHCOCH3). C12H12FIN2O3, LCMS (EI) m/e 379 (M++H).

Workup

  1. customthe resulting reaction mixture
  2. customThe resulting reaction mixture
  3. customthe reaction mixture was quenched with H2O (100 mL)
  4. customThe two layers were separated
  5. extractionthe aqueous layer was extracted with CH2Cl2 (2×50 mL)
  6. washThe combined organic extracts were washed with H2O (2×100 mL) and saturated aqueous NaCl (100 mL)
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated in vacuo
  9. customThe residue was further dried in vacuo

Sources & evidence

ORD record
ord-58a72be5fbf9437e8e4c28d2cf466d88
Source dataset
uspto-grants-2012_12
Patent number
US08324398B2

Reaction notes

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