5-Bromo-2-methoxycyclohepta-2,4,6-trien-1-one → (S)-N-[[3-[3-fluoro-4-(4-methoxy-5-oxo-1,3,6-cycloheptatrien-1-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide

HRID 259818Notes

Reaction equation

HRID 259818 reaction equation
[I-].O1CCNC1=O.[F:8][C:9]1[CH:10]=[C:11]([N:19]2[CH2:23][C@H:22]([CH2:24][NH:25][C:26](=[O:28])[CH3:27])[O:21][C:20]2=[O:29])[CH:12]=[CH:13][C:14]=1[Sn](C)(C)C.Br[C:31]1[CH:37]=[CH:36][C:35](=[O:38])[C:34]([O:39][CH3:40])=[CH:33][CH:32]=1>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:8][C:9]1[CH:10]=[C:11]([N:19]2[CH2:23][C@H:22]([CH2:24][NH:25][C:26](=[O:28])[CH3:27])[O:21][C:20]2=[O:29])[CH:12]=[CH:13][C:14]=1[C:31]1[CH:37]=[CH:36][C:35](=[O:38])[C:34]([O:39][CH3:40])=[CH:33][CH:32]=1

Participants

6

Reactant 3

HCID 6040175-Bromo-2-methoxycyclohepta-2,4,6-trien-1-oneHCID 11304566N-({(5S)-3-[3-Fluoro-4-(trimethylstannyl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamideHCID 21585223Oxazolidinone iodide

Product 1

HCID 44264058(S)-N-[[3-[3-fluoro-4-(4-methoxy-5-oxo-1,3,6-cycloheptatrien-1-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamideYield 57%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

Alternatively, the oxazolidinone iodide described above can be converted to (S)-N-[[3-[3-fluoro-4-(trimethylstannyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide, employing conditions disclosed for the corresponding racemic material in TR 7246-92-050. This tin-substituted intermediate (0.180 g, 0.43 mmol) and 5-bromo-2-methoxycyclohepta-2,4,6-trien-1-one (0.103 g, 0.48 mmol) were dissolved in dry DMF (3 mL) and the resultant solution degassed by repeated evacuation and filling with nitrogen. Bis(triphenylphosphine)palladium(II) chloride (0.015 g, 0.02 mmol) was added, the reaction again degassed, and the mixture heated to 80° C. for 2 h. TLC revealed some starting material still remained, so additional palladium catalyst (0.015 g) was added and the mixture heated a further 5 h. The reaction mixture was concentrated in vacuo and the residue chromatographed over silica gel, eluting with a methanol/chloroform gradient, to afford 0.096 g (57%) of the title compound, identical in all respects to material prepared via the above protocol.

Workup

  1. customthe resultant solution degassed
  2. customthe reaction
  3. customagain degassed
  4. additionso additional palladium catalyst (0.015 g) was added
  5. temperaturethe mixture heated a further 5 h
  6. concentrationThe reaction mixture was concentrated in vacuo
  7. customthe residue chromatographed over silica gel
  8. washeluting with a methanol/chloroform gradient

Sources & evidence

ORD record
ord-4ef58245437d4a36be9605774cc6e5b7
Source dataset
uspto-grants-1996_06
Patent number
US05523403

Reaction notes

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