Triphenylarsine → 5(R)-isoxazol-3-yloxymethyl-3-(4-{8-tert-butyloxycarbonyl-8-azabicyclo[3.2.1]oct-2-ene-3-yl}-3-fluorophenyl)oxazolidin-2-one

HRID 1167504Notes

Reaction equation

HRID 1167504 reaction equation
C1([As](C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cl-].[Li+].[O:22]1[CH:26]=[CH:25][C:24]([O:27][CH2:28][C@@H:29]2[O:33][C:32](=[O:34])[N:31]([C:35]3[CH:40]=[CH:39][C:38](I)=[C:37]([F:42])[CH:36]=3)[CH2:30]2)=[N:23]1.[C:43]([O:47][C:48]([N:50]1[CH:55]2[CH2:56][CH2:57][CH:51]1[CH:52]=[C:53]([Sn](C)(C)C)[CH2:54]2)=[O:49])([CH3:46])([CH3:45])[CH3:44].[F-].[K+]>CN(C=O)C.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[O:22]1[CH:26]=[CH:25][C:24]([O:27][CH2:28][C@@H:29]2[O:33][C:32](=[O:34])[N:31]([C:35]3[CH:40]=[CH:39][C:38]([C:53]4[CH2:54][CH:55]5[N:50]([C:48]([O:47][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:49])[CH:51]([CH2:57][CH2:56]5)[CH:52]=4)=[C:37]([F:42])[CH:36]=3)[CH2:30]2)=[N:23]1

Participants

8

Reactant 5

HCID 11773TriphenylarsineHCID 433294Lithium ChlorideHCID 522689Potassium FluorideHCID 118590405(R)-isoxazol-3-yloxymethyl-3-(3-fluoro-4-iodophenyl)oxazolidin-2-oneHCID 22647946Tert-butyl 3-(trimethylstannyl)-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylate

Product 1

HCID 213566705(R)-isoxazol-3-yloxymethyl-3-(4-{8-tert-butyloxycarbonyl-8-azabicyclo[3.2.1]oct-2-ene-3-yl}-3-fluorophenyl)oxazolidin-2-one

Reagents, catalysts & solvents 2

HCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalystHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
60 °C

Procedure

Tris(dibenzylideneacetone) dipalladium(0) (0.19 g, 0.208 mmol), triphenylarsine (0.13 g, 0.425 mmol) and lithium chloride (0.265 g, 6.31 mmol) were added to a stirred solution of 5(R)-isoxazol-3-yloxymethyl-3-(3-fluoro-4-iodophenyl)oxazolidin-2-one (prepared by analogy to reference Example 28) (0.85 g, 2.1 mmol) in degassed DMF (35 ml) under nitrogen. After 5 minutes, a solution of 8-tert-butyloxycarbonyl-3-trimethylstannyl-8-azabicyclo[3.2.1]oct-2-ene (GB 2298647; 0.78 g, 2.1 mmol) in DMF (4 ml) was added and the mixture was heated at 60° C. for 18 hours. A solution of 2M potassium fluoride (30 ml) was added and the mixture stirred for 40 minutes. Solvent was evaporated and the residue partitioned between water and EtOAc. The aqueous layer was extracted twice with EtOAc and the combined extracts dried (Na2SO4) and evaporated. The residue was purified by column chromatography, eluting with a gradient of dichloromethane-5% MeOH/dichloromethane to give 5(R)-isoxazol-3-yloxymethyl-3-(4-{8-tert-butyloxycarbonyl-8-azabicyclo[3.2.1]oct-2-ene-3-yl }-3-fluorophenyl)oxazolidin-2-one as an oil of 85% purity [hplc](0.97 g, 81%). MS: 486 (MH+).

Workup

  1. customSolvent was evaporated
  2. customthe residue partitioned between water and EtOAc
  3. extractionThe aqueous layer was extracted twice with EtOAc
  4. dry with materialthe combined extracts dried (Na2SO4)
  5. customevaporated
  6. customThe residue was purified by column chromatography
  7. washeluting with a gradient of dichloromethane-5% MeOH/dichloromethane

Sources & evidence

ORD record
ord-9d111d41df3444abbc7ea6e0f0926420
Source dataset
uspto-grants-2003_09
Patent number
US06617339B1

Reaction notes

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