Hydrochloric Acid → Ethyl 5-chloro-2-(2,3-difluoro-6-methoxybenzyloxy)-4-nitrocinnamate

HRID 1513013Notes

Reaction equation

HRID 1513013 reaction equation
Br[C:2]1[C:7]([O:8][CH2:9][C:10]2[C:15]([O:16][CH3:17])=[CH:14][CH:13]=[C:12]([F:18])[C:11]=2[F:19])=[CH:6][C:5]([N+:20]([O-:22])=[O:21])=[C:4]([Cl:23])[CH:3]=1.[C:24]([O:28][CH2:29][CH3:30])(=[O:27])[CH:25]=[CH2:26].CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.Cl>C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(N(CC)CC)C>[Cl:23][C:4]1[C:5]([N+:20]([O-:22])=[O:21])=[CH:6][C:7]([O:8][CH2:9][C:10]2[C:15]([O:16][CH3:17])=[CH:14][CH:13]=[C:12]([F:18])[C:11]=2[F:19])=[C:2]([CH:3]=1)[CH:26]=[CH:25][C:24]([O:28][CH2:29][CH3:30])=[O:27]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 8821Ethyl AcrylateHCID 80271Tri-o-tolylphosphineHCID 685153834-Bromo-2-chloro-5-(2,3-difluoro-6-methoxybenzyloxy)-1-nitrobenzene

Product 1

HCID 68514028Ethyl 5-chloro-2-(2,3-difluoro-6-methoxybenzyloxy)-4-nitrocinnamate

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolventHCID 8471TriethylamineSolvent

Procedure

A mixture of 4-bromo-2-chloro-5-(2,3-difluoro-6-methoxybenzyloxy)-1-nitrobenzene (3.06 g), ethyl acrylate (1.64 mL), palladium(II) acetate (84 mg), tris(2-methylphenyl)phosphine (0.23 g) and triethylamine (5.2 mL) in acetonitrile (30 mL) was heated at reflux overnight. The reaction mixture was cooled to room temperature, and poured into 1 mol/L hydrochloric acid, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=4/1−2/1) to give ethyl 5-chloro-2-(2,3-difluoro-6-methoxybenzyloxy)-4-nitrocinnamate (2.46 g). This material was dissolved in tetrahydrofuran (30 mL). To the solution were added methanol (30 mL) and nickel(II) bromide (63 mg). To the mixture was added sodium borohydride (0.65 g) under ice-cooling, and the mixture was stirred at the same temperature for 30 minutes, and then stirred at room temperature for 30 minutes. The reaction mixture was poured into a saturated aqueous sodium hydrogen carbonate solution, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=4/1−1/1) to give the title compound (0.69 g).

Workup

  1. temperaturewas heated
  2. temperatureat reflux overnight
  3. extractionthe resulting mixture was extracted with ethyl acetate
  4. washThe extract was washed with water and brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThe solvent was removed under reduced pressure
  7. customthe residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=4/1−2/1)

Sources & evidence

ORD record
ord-ba9727349bfd492a84534f64315817b7
Source dataset
uspto-grants-2012_07
Patent number
US08217069B2

Reaction notes

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