HCID 86726354, compound → HCID 86726353, compound

HRID 629751Notes

Reaction equation

HRID 629751 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([Mg]Br)=[CH:4][CH:3]=1.[F:10][C:11]1[CH:12]=[C:13](/[CH:18]=[CH:19]/[C:20]([N:22]2[C@H:26]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH2:25][O:24][C:23]2=[O:33])=[O:21])[CH:14]=[C:15]([F:17])[CH:16]=1>C1COCC1>[F:10][C:11]1[CH:12]=[C:13]([C@H:18]([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)[CH2:19][C:20]([N:22]2[C@H:26]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH2:25][O:24][C:23]2=[O:33])=[O:21])[CH:14]=[C:15]([F:17])[CH:16]=1

Participants

4

Reactant 2

HCID 86726354HCID 86726354, compoundHCID 178418676HCID 178418676, compound

Product 1

HCID 86726353HCID 86726353, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-40 °C

Procedure

A solution of 4-fluorophenylmagnesium bromide (29 mL of a 2.0 M solution in THF, 58 mmol) and copper(I) bromide-dimethylsulfide complex (12 g, 59 mmol) in THF (100 mL) under an atmosphere of nitrogen was cooled to −40° C. in a dry ice-acetonitrile bath. To the stirred solution was added a solution of (4R)-3-[(2E)-3-(3,5-difluorophenyl)prop-2-enoyl]-4-phenyl-1,3-oxazolidin-2-one (7.7 g, 23 mmol) in 100 mL of THF dropwise over 15 min. The resulting mixture was stirred at −40° C. for 1.5 h, then the cooling bath was removed and the stirred mixture was allowed to warm to ambient temperature. The reaction was quenched by the addition of aqueous NH4Cl solution. The resulting mixture was stirred for 15 min then extracted with two portions of EtOAc. The combined organic phases were washed with water and brine, then dried (MgSO4), filtered, and the solvents were removed in vacuo. The residue was chromatographed on a 330 g SiO2 column using a gradient elution of 0-50% EtOAc:A, where A=1:1 hexanes:CHCl3. Fractions containing product were combined and the solvents were removed in vacuo to give a solid.

Workup

  1. customthe cooling bath was removed
  2. temperatureto warm to ambient temperature
  3. customThe reaction was quenched by the addition of aqueous NH4Cl solution
  4. stirringThe resulting mixture was stirred for 15 min
  5. extractionthen extracted with two portions of EtOAc
  6. washThe combined organic phases were washed with water and brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. customthe solvents were removed in vacuo
  10. customThe residue was chromatographed on a 330 g SiO2 column
  11. washa gradient elution of 0-50% EtOAc
  12. additionFractions containing product
  13. customthe solvents were removed in vacuo
  14. customto give a solid

Sources & evidence

ORD record
ord-614fb9de5929485cbecfdda1d5cbcf1b
Source dataset
uspto-grants-2016_04
Patent number
US09315475B2

Reaction notes

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