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

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

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.