Hydrochloric Acid → Cyano-(4-methoxy-5-methyl-2-nitrophenyl)acetic acid methyl ester

HRID 881607Notes

Reaction equation

HRID 881607 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5](=[O:9])[CH2:6][C:7]#[N:8].F[C:11]1[CH:16]=[C:15]([CH3:17])[C:14]([O:18][CH3:19])=[CH:13][C:12]=1[N+:20]([O-:22])=[O:21].Cl>CN(C)C=O>[CH3:3][O:4][C:5](=[O:9])[CH:6]([C:7]#[N:8])[C:11]1[CH:16]=[C:15]([CH3:17])[C:14]([O:18][CH3:19])=[CH:13][C:12]=1[N+:20]([O-:22])=[O:21]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 7747Methyl cyanoacetateHCID 24758Sodium hydrideHCID 598501391-Fluoro-4-methoxy-5-methyl-2-nitrobenzene

Product 1

HCID 58437260Cyano-(4-methoxy-5-methyl-2-nitrophenyl)acetic acid methyl esterYield 71.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a suspension of sodium hydride (0.86 g) in N,N-dimethylformamide (5 mL) was added dropwise a solution of cyano acetic acid methyl ester (0.35 g) in N,N-dimethylformamide (3 mL) under ice cooling and this mixture was stirred for 15 minutes. To this reaction mixture was added dropwise a solution of 1-fluoro-4-methoxy-5-methyl-2-nitrobenzene (0.44 g) under ice cooling and this mixture was stirred at room temperature for 30 minutes, and then stirred at 70° C. overnight. After cooling to ambient temperature, 1 mol/L hydrochloric acid (5 mL) was added to this reaction mixture. This resulting mixture was extracted with ethyl acetate. This organic layer was washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate) to give the title compound (0.45 g).

Workup

  1. stirringthis mixture was stirred at room temperature for 30 minutes
  2. stirringstirred at 70° C. overnight
  3. extractionThis resulting mixture was extracted with ethyl acetate
  4. washThis organic layer was washed with water and brine
  5. dry with materialdried over anhydrous magnesium 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)

Sources & evidence

ORD record
ord-4b6458604fee42cd967e4847facbd396
Source dataset
uspto-grants-2015_03
Patent number
US08993616B2

Reaction notes

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