Tetrahydrofuran → Methyl 5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)-2-(3,4-difluorophenyl)-3-oxo-2,3-dihydrofuro[2,3-b]pyridine-2-carboxylate

HRID 8802Notes

Reaction equation

HRID 8802 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]([C:36]#N)[C:11]([O:22][CH:23]([C:28]3[CH:33]=[CH:32][C:31]([F:34])=[C:30]([F:35])[CH:29]=3)[C:24]([O:26][CH3:27])=[O:25])=[N:12][C:13]=2[C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=2[Cl:21])=[CH:4][CH:3]=1.C[Si]([NH-])(C)C.C[Si]([NH-])(C)C.[Li+].[Li+].C1C[O:53]CC1>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:9]=[C:10]3[C:36](=[O:53])[C:23]([C:28]4[CH:33]=[CH:32][C:31]([F:34])=[C:30]([F:35])[CH:29]=4)([C:24]([O:26][CH3:27])=[O:25])[O:22][C:11]3=[N:12][C:13]=2[C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=2[Cl:21])=[CH:6][CH:7]=1

Participants

4

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 86588160Lithim bis(trimethylsilylamide)HCID 86602010Methyl {[5-(4-chlorophenyl)-3-cyano-6-(2,4-dichlorophenyl)pyridin-2-yl]oxy}(3,4-difluorophenyl)acetate

Product 1

HCID 21984819Methyl 5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)-2-(3,4-difluorophenyl)-3-oxo-2,3-dihydrofuro[2,3-b]pyridine-2-carboxylate

Procedure

To a magnetically stirred solution of 1.20 g (2.14 mmol) the product of Step A dissolved in 12 mL of THF was slowly added 3.2 mL of a 1.0 N solution (3.2 mmol) of lithium bis(trimethylsilylamide) in THF at 0° C. The reaction mixture was stirred for 30 min and allowed to warm to room temperature. The reaction mixture was then quenched by addition of excesss 10% aqueous NaHSO4 and extracted into EtOAc. The organic layer was separated, washed with water, dried (MgSO4), filtered and evaporated. The residue was purified on a silica gel flash chromatography column eluted with chloroform. Combination of the purified fractions and drying in vacuo afforded the title compound.

Workup

  1. customat 0° C
  2. customThe reaction mixture was then quenched by addition of excesss 10% aqueous NaHSO4
  3. extractionextracted into EtOAc
  4. customThe organic layer was separated
  5. washwashed with water
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified on a silica gel flash chromatography column
  10. washeluted with chloroform
  11. customCombination of the purified fractions and drying in vacuo

Sources & evidence

ORD record
ord-56f0e6a441a9460baf2227bb5042856e
Source dataset
uspto-grants-2006_08
Patent number
US07091216B2

Reaction notes

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