Cesium carbonate → (RS)-N-[4-cyano-2-(5-nitro-pyridin-2-yloxy)-benzyl]-2-ethoxy-2-(2-fluoro-4-methoxy-phenyl)-acetamide

HRID 1247350Notes

Reaction equation

[C:1]([C:3]1[CH:25]=[CH:24][C:6]([CH2:7][NH:8][C:9](=[O:23])[CH:10]([O:20][CH2:21][CH3:22])[C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][C:12]=2[F:19])=[C:5]([OH:26])[CH:4]=1)#[N:2].Cl[C:28]1[CH:33]=[CH:32][C:31]([N+:34]([O-:36])=[O:35])=[CH:30][N:29]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O>[C:1]([C:3]1[CH:25]=[CH:24][C:6]([CH2:7][NH:8][C:9](=[O:23])[CH:10]([O:20][CH2:21][CH3:22])[C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][C:12]=2[F:19])=[C:5]([O:26][C:28]2[CH:33]=[CH:32][C:31]([N+:34]([O-:36])=[O:35])=[CH:30][N:29]=2)[CH:4]=1)#[N:2]

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of (RS)-N-(4-cyano-2-hydroxy-benzyl)-2-ethoxy-2-(2-fluoro-4-methoxy-phenyl)-acetamide (310 mg) and 2-chloro-5-nitropyridine (205 mg) in DMSO (2 ml) was added cesium carbonate (423 mg). The mixture was stirred at 50° C. for 5 h. The solvent was evaporated, the residue was dissolved in EtOAc and washed with water (2×) and brine (1×). The organic phase was dried, filtered and concentrated. The product was purified by flash chromatography (cyclohexane/EtOAc 9:1=>4:6) to give (RS)-N-[4-cyano-2-(5-nitro-pyridin-2-yloxy)-benzyl]-2-ethoxy-2-(2-fluoro-4-methoxy-phenyl)-acetamide. Light yellow foam. MS 481.4 ([M+H]+)

Workup

customThe solvent was evaporated
dissolutionthe residue was dissolved in EtOAc
washwashed with water (2×) and brine (1×)
customThe organic phase was dried
filtrationfiltered
concentrationconcentrated
customThe product was purified by flash chromatography (cyclohexane/EtOAc 9:1=>4:6)

Sources & evidence

ORD record: ord-b23236889bfa414ab742550ce79d4026
Source dataset: uspto-grants-2006_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07129238B2

Reaction notes

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