Methyl 2-acetamidoacrylate → 2-Acetylamino-3-(2-[1,3]dioxan-2-yl-3-fluoro-phenyl)-acrylic acid methyl ester

HRID 2245284Notes

Reaction equation

HRID 2245284 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4](I)[C:3]=1[CH:9]1[O:14][CH2:13][CH2:12][CH2:11][O:10]1.[CH3:15][O:16][C:17](=[O:24])[C:18]([NH:20][C:21](=[O:23])[CH3:22])=[CH2:19].C(=O)(O)[O-].[Na+]>[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C=O)C>[CH3:15][O:16][C:17](=[O:24])[C:18]([NH:20][C:21](=[O:23])[CH3:22])=[CH:19][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=1[CH:9]1[O:14][CH2:13][CH2:12][CH2:11][O:10]1

Participants

7

Reactant 3

HCID 98644Methyl 2-acetamidoacrylateHCID 516892Sodium BicarbonateHCID 685501032-(2-Fluoro-6-iodo-phenyl)-[1,3]dioxane

Product 1

HCID 685501862-Acetylamino-3-(2-[1,3]dioxan-2-yl-3-fluoro-phenyl)-acrylic acid methyl esterYield 12.4%

Reagents, catalysts & solvents 3

HCID 70681Tetrabutylammonium ChlorideCatalystHCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Procedure

A DMF (10 ml) solution of 2-(2-fluoro-6-iodo-phenyl)-[1,3]dioxane (1.85 g, 6 mmol), 2-acetylamino-acrylic acid methyl ester (906 mg, 6.33 mmol), sodium bicarbonate (1.26 g, 15 mmol), tetrabutyl ammonium chloride (1.35 g, 4.86 mmol) and palladium (II) acetate (52 mg, 0.23 mmol) is heated at 90° C. for 1.8 hours. The reaction mixture is poured onto water and the aqueous phase is extracted with ethylacetate. The organic layer is washed with brine and dried over MgSO4 and evaporated. The crude product is purified by chromatography (CH2Cl2/MeOH, 95/5) to afford the desired compound (240 mg). MS (ES+): m/e=346.3, (MNa+)

Workup

  1. additionThe reaction mixture is poured onto water
  2. extractionthe aqueous phase is extracted with ethylacetate
  3. washThe organic layer is washed with brine
  4. dry with materialdried over MgSO4
  5. customevaporated
  6. customThe crude product is purified by chromatography (CH2Cl2/MeOH, 95/5)

Sources & evidence

ORD record
ord-381a067d5259455dae0a8904179e7689
Source dataset
uspto-grants-2010_03
Patent number
US07683075B2

Reaction notes

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