Ethyl Acetate → HCID 66810467, compound

HRID 1097511Notes

Reaction equation

HRID 1097511 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([OH:9])[CH:5]=[CH:6][C:7]=1[F:8].C(=O)([O-])O.[Na+].[Cl:15][C:16]1[C:24]([C:25]([C:28]#[N:29])([CH3:27])[CH3:26])=[CH:23][CH:22]=[CH:21][C:17]=1[C:18](Cl)=[O:19].C(OCC)(=O)C>O1CCCC1.O>[Cl:15][C:16]1[C:24]([C:25]([C:28]#[N:29])([CH3:27])[CH3:26])=[CH:23][CH:22]=[CH:21][C:17]=1[C:18]([NH:1][C:2]1[CH:3]=[C:4]([OH:9])[CH:5]=[CH:6][C:7]=1[F:8])=[O:19]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 135191803-Amino-4-fluorophenolHCID 86644704HCID 86644704, compound

Product 1

HCID 66810467HCID 66810467, compoundYield 97%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

2-Chloro-3-(1-cyano-1-methylethyl)benzoic acid (3.0 g, 13.4 mmol) was dissolved in tetrahydrofuran (67 mL), and oxalyl chloride (1.35 mL, 15.8 mmol) and N,N-dimethylformamide (20 μL) were added. The reaction mixture was stirred at room temperature for 1 hr, and the solvent was evaporated under reduced pressure to give 2-chloro-3-(1-cyano-1-methylethyl)benzoyl chloride. To a solution of 3-amino-4-fluorophenol (1.62 g, 12.8 mmol) in tetrahydrofuran (20 ml) was added a suspension of sodium hydrogen carbonate (3.22 g, 38.3 mmol) in water (40 mL), and the mixture was vigorously stirred at room temperature. To this mixture was added dropwise at 0° C. a solution of 2-chloro-3-(1-cyano-1-methylethyl)benzoyl chloride produced above in tetrahydrofuran (20 mL), and the mixture was stirred at room temperature for 2 hr. To the reaction mixture was added ethyl acetate (100 mL), and the aqueous layer was separated. The organic layer was washed with saturated brine (150 mL), and dried over anhydrous sodium sulfate. Insoluble material was filtered off, and the filtrate was purified by basic silica gel column chromatography (eluate: ethyl acetate). The obtained solution was concentrated under reduced pressure, and the obtained residue was crystallized from ethyl acetate/n-hexane to give the title compound (4.13 g, 97%) as a white powder.

Workup

  1. stirringthe mixture was stirred at room temperature for 2 hr
  2. customthe aqueous layer was separated
  3. washThe organic layer was washed with saturated brine (150 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationInsoluble material was filtered off
  6. customthe filtrate was purified by basic silica gel column chromatography (eluate: ethyl acetate)
  7. concentrationThe obtained solution was concentrated under reduced pressure
  8. customthe obtained residue was crystallized from ethyl acetate/n-hexane

Sources & evidence

ORD record
ord-2c30e18b2f1c439dae02fdd53328df3e
Source dataset
uspto-grants-2012_03
Patent number
US08143258B2

Reaction notes

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