Water → HCID 11433143, compound

HRID 915294Notes

Reaction equation

HRID 915294 reaction equation
Cl[CH:2]([O:4][C:5](=[O:32])[N:6]([C:29](=[O:31])[CH3:30])[CH2:7][C@@H:8]1[O:12][C:11](=[O:13])[N:10]([C:14]2[CH:19]=[CH:18][C:17]([CH:20]3[CH2:25][CH2:24][S:23](=[O:27])(=[O:26])[CH2:22][CH2:21]3)=[C:16]([F:28])[CH:15]=2)[CH2:9]1)[CH3:3].[C:33]([O-:41])(=[O:40])[C:34]1[CH:39]=[CH:38][N:37]=[CH:36][CH:35]=1.[Cs+].O>C(#N)C>[C:29]([N:6]([CH2:7][C@@H:8]1[O:12][C:11](=[O:13])[N:10]([C:14]2[CH:19]=[CH:18][C:17]([CH:20]3[CH2:25][CH2:24][S:23](=[O:27])(=[O:26])[CH2:22][CH2:21]3)=[C:16]([F:28])[CH:15]=2)[CH2:9]1)[C:5]([O:4][CH:2]([O:41][C:33](=[O:40])[C:34]1[CH:39]=[CH:38][N:37]=[CH:36][CH:35]=1)[CH3:3])=[O:32])(=[O:31])[CH3:30]

Participants

5

Reactant 3

HCID 962WaterHCID 23698454HCID 23698454, compoundHCID 58958558HCID 58958558, compound

Product 1

HCID 11433143HCID 11433143, compoundYield 83%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Acetyl-{3-[4-(1,1-dioxo-hexahydro-1λ6-thiopyran-4-yl)-3-fluoro-phenyl]-2-oxo-oxazolidin-5(R)-ylmethyl}-carbamic acid 1-chloro-ethyl ester (11) (0.40 g, 0.81 mmol) and cesium isonicotinate (0.42 g, 1.64 mmol) in acetonitrile (20 mL) are heated to reflux overnight. After cooling to RT, water is added and the reaction mixture is extracted with EtOAc and then with dichloromethane. The organic phases are washed separately with brine and then the organic layers are combined, dried over MgSO4, filtered, and conc in vacuo. The isolated residue is subjected to silica gel flash chromatography, eluting with MeOH/CH2Cl2 gradient (0-5% MeOH over 1 hour and 20 minutes) to afford the title compound. Isolated yield: 83%. 1H NMR (400 MHz, DMSO-d6): δ 8.78-8.74 (m, 2H), 7.85 (dd, 1H), 7.79 (dd, 1H), 7.40-7.35 (m, 1H), 7.31 (t, 1H), 7.21-7.17 (m, 1H), 7.01-6.94 (m, 1H), 4.79-4.72 (m, 1H), 4.12-4.00 (m, 2H), 3.91-3.84 (m, 1H), 3.78-3.73 (m, 1H), 3.36-3.26 (m, partially obscured by water, 2H), 3.17-3.11 (m, 1H), 3.07-3.03 (m, 2H), 2.40 (d, 3H), 2.15-2.04 (m, 2H), 2.00-1.97 (m, 2H) 1.59 (dd, 3H).

Workup

  1. temperatureto reflux overnight
  2. extractionthe reaction mixture is extracted with EtOAc
  3. washThe organic phases are washed separately with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. washeluting with MeOH/CH2Cl2 gradient (0-5% MeOH over 1 hour and 20 minutes)

Sources & evidence

ORD record
ord-e5c10b5090bc48f497c85e0810a1438d
Source dataset
uspto-grants-2007_09
Patent number
US07265140B2

Reaction notes

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