1,1'-Carbonyldiimidazole → 3-[3-fluoro-4-(4-oxo-3,4-dihydro-2H-pyridin-1-yl)phenyl]-2-oxo-5-oxazolidinecarboxylic acid ethyl ester

HRID 723900

Reaction equation

HRID 723900 reaction equation
C1N=CN([C:6](N2C=NC=C2)=[O:7])C=1.[CH2:13]([O:15][C:16](=[O:35])[C@H:17]([OH:34])[CH2:18][NH:19][C:20]1[CH:25]=[CH:24][C:23]([N:26]2[CH:31]=[CH:30][C:29](=[O:32])[CH2:28][CH2:27]2)=[C:22]([F:33])[CH:21]=1)[CH3:14]>C(#N)C>[CH2:13]([O:15][C:16]([CH:17]1[O:34][C:6](=[O:7])[N:19]([C:20]2[CH:25]=[CH:24][C:23]([N:26]3[CH:27]=[CH:28][C:29](=[O:32])[CH2:30][CH2:31]3)=[C:22]([F:33])[CH:21]=2)[CH2:18]1)=[O:35])[CH3:14]

Participants

4

Reactant 2

HCID 682631,1'-CarbonyldiimidazoleHCID 684871023-[3-fluoro-4-(4-oxo-3,4-dihydro-2H-pyridin-1-yl)phenylamino]-2(R)-hydroxypropionic acid ethyl ester

Product 1

HCID 684890643-[3-fluoro-4-(4-oxo-3,4-dihydro-2H-pyridin-1-yl)phenyl]-2-oxo-5-oxazolidinecarboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

CDI (162.0 mg, 1.0 mmol) is added with stirring to a solution of 3-[3-fluoro-4-(4-oxo-3,4-dihydro-2H-pyridin-1-yl)phenylamino]-2(R)-hydroxypropionic acid ethyl ester (Step 5, 146.0 mg, 0.45 mmol) in acetonitrile (4.0 mL), and the mixture is stirred at room temperature overnight. Solvent is removed under vacuum, and the residue partitioned between EtOAc (30 mL) and aq. 3% citric acid (30 mL). The aqueous layer is extracted with EtOAc (2×30 mL), and the combined organic layers are washed with water and saline and dried (MgSO4). EtOAc is removed under vacuum to afford the crude 3-[3-fluoro-4-(4-oxo-3,4-dihydro-2H-pyridin-1-yl)phenyl]-2-oxo-5-oxazolidinecarboxylic acid ethyl ester which is used in the next step w/o further purification (MS (m/z): 349 [M+H]+). The ester intermediate is taken up in 2M methanolic ammonia (8.0 mL, 16.0 mmol), and the resulting solution heated in a closed vial at 60° C. for 1 h. Volatiles are removed under vacuum, and the crude material purified by silica gel chromatography (eluent: 2% MeOH in CH2Cl2) to afford the title compound (55.0 mg, 38% for two steps) as white crystals, MS for C15H14FN3O4 m/z 320 (M+H)+; 1H NMR (CD3CN): δ 2.51 (m, 2H), 3.89 (m, 2H), 4.05 (m, 1H), 4.24 (dd, 1H), 4.97 (m, 1H), 5.03 (d, 1H), 6.18 (br. s, 1H), 6.72 (br. s, 1H), 7.20–7.40 (m, 3H), 7.57 (d, 1H).

Workup

  1. customSolvent is removed under vacuum
  2. customthe residue partitioned between EtOAc (30 mL) and aq. 3% citric acid (30 mL)
  3. extractionThe aqueous layer is extracted with EtOAc (2×30 mL)
  4. washthe combined organic layers are washed with water and saline
  5. dry with materialdried (MgSO4)
  6. customEtOAc is removed under vacuum

Sources & evidence

ORD record
ord-1d34d5c3f58c457c9d9e18c59cdee887
Source dataset
uspto-grants-2006_11
Patent number
US07141588B2

Linked notes

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