Ethyl Acetate → (5R,5'R)-4,4'-Bis-(5-(1H-1,2,3-triazol-1-yl)methyl-2-oxo-oxazolidin-3-yl)-2,2'-difluoro-biphenyl

HRID 747217Notes

Reaction equation

HRID 747217 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:12]2[CH2:16][C@H:15]([CH2:17][N:18]3[CH:22]=[CH:21][N:20]=[N:19]3)[O:14][C:13]2=[O:23])[CH:5]=[CH:6][C:7]=1[Sn](C)(C)C.Br[C:25]1S[C:27]([C:30]#N)=[CH:28][N:29]=1.[F-:32].[K+].[C:34]([O:37][CH2:38][CH3:39])(=[O:36])C>CN(C)C=O.CS(C)=O.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N:18]1([CH2:17][C@@H:15]2[O:14][C:13](=[O:23])[N:12]([C:4]3[CH:5]=[CH:6][C:7]([C:7]4[CH:30]=[CH:27][C:28]([N:29]5[CH2:25][C@H:38]([CH2:39][N:18]6[CH:22]=[CH:21][N:20]=[N:19]6)[O:37][C:34]5=[O:36])=[CH:3][C:2]=4[F:32])=[C:2]([F:1])[CH:3]=3)[CH2:16]2)[CH:22]=[CH:21][N:20]=[N:19]1

Participants

9

Reactant 4

HCID 8857Ethyl AcetateHCID 522689Potassium FluorideHCID 11212438(5R)-3-(3-fluoro-4-(trimethylstannyl)phenyl)-5-(1H-1,2,3-triazol-1-ylmethyl)-1,3-oxazolidin-2-oneHCID 178609522-Bromo-1,3-thiazole-5-carbonitrile

Product 1

HCID 59749424(5R,5'R)-4,4'-Bis-(5-(1H-1,2,3-triazol-1-yl)methyl-2-oxo-oxazolidin-3-yl)-2,2'-difluoro-biphenyl

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 679Dimethyl SulfoxideSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A stirred mixture of (5R)-3-(3-fluoro-4-(trimethylstannyl)phenyl)-5-(1H-1,2,3-triazol-1-ylmethyl)-1,3-oxazolidin-2-one (425 mg, 1.0 mmol), 2-bromo-5-cyano-thiazole (189 mg, 1.0 mmol, and copper(I) iodide in dimethylformamide (5 ml) was purged with a slow stream of nitrogen for 20 min and then tetrakis(triphenylphosphine)palladium(0) (58 mg, 0.05 mmol) was added. The stirred reaction mixture was maintained at 70° C. under an atmosphere of nitrogen for 5 hours. The stirred reaction mixture was treated with aqueous potassium fluoride (10%, 20 ml) and then stirred for 30 min, treated with ethyl acetate (20 ml). The precipitate was isolated by filtration to give fraction A of impure product. The organic phase was separated, dried (MgSO4), treated with silica-gel (500 mg), and evaporated under reduced pressure to leave a free-running solid. The solid was applied to a silica-gel column and eluted with dichloromethane-methanol (0%-10% methanol gradient) to give a further fraction B of impure product. Fractions A and B were dissolved in DMSO (6 ml total), combined, and purified by reverse phase hplc to give the desired product (18 mg).

Workup

  1. customwas purged with a slow stream of nitrogen for 20 min
  2. customThe stirred reaction mixture
  3. customThe stirred reaction mixture
  4. customThe precipitate was isolated by filtration
  5. customto give fraction A of impure product
  6. customThe organic phase was separated
  7. dry with materialdried (MgSO4)
  8. additiontreated with silica-gel (500 mg)
  9. customevaporated under reduced pressure
  10. customto leave a free-running solid
  11. washeluted with dichloromethane-methanol (0%-10% methanol gradient)
  12. customto give a further fraction B of impure product
  13. custompurified by reverse phase

Sources & evidence

ORD record
ord-89beed8c02934b43b0efbed7570f01c6
Source dataset
uspto-grants-2008_07
Patent number
US07396847B2

Reaction notes

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