Ethyl Acetate → Ethyl phenylmethyl (2-fluoro-4-nitrophenyl)propanedioate

HRID 889483Notes

Reaction equation

HRID 889483 reaction equation
[C:1]([O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)(=[O:8])[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[H-].[Na+].[F:19][C:20]1[CH:21]=[C:22]([N+:27]([O-:29])=[O:28])[CH:23]=[CH:24][C:25]=1F.C(OCC)(=O)C>CN(C=O)C.CCCCCC>[F:19][C:20]1[CH:21]=[C:22]([N+:27]([O-:29])=[O:28])[CH:23]=[CH:24][C:25]=1[CH:2]([C:1]([O:9][CH2:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)=[O:8])[C:3]([O:5][CH2:6][CH3:7])=[O:4]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 1230531,2-Difluoro-4-nitrobenzeneHCID 562228Benzyl ethyl malonate

Product 1

HCID 59760054Ethyl phenylmethyl (2-fluoro-4-nitrophenyl)propanedioateYield 84.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8058HexaneSolvent

Procedure

Benzyl ethyl malonate (2.9 g, 12.6 mmol) in dry DMF (20 ml) was cooled in an ice bath and the temperature monitored whilst sodium hydride (504 mg, 12.6 mmol) was added portionwise. This was stirred at room temperature for 10 minutes until H2 evolution ceased. 3,4-Difluoronitrobenzene (2 g, 12.6 mmol) was added under an argon atmosphere and gave a dark red colour change. The reaction mixture was heated at 100° C. for 20 hours under argon. Thin layer chromatography (20% ethyl acetate in hexane) showed completion of the reaction. The reaction mixture was cooled to room temperature and partitioned between 2N Hydrochloric acid (75 ml) and ethyl acetate (75 ml). The aqueous layer was extracted with ethyl acetate (2×75 ml) and the combined organic fractions were evaporated to a yellow oil. Purification by chromatography on silica gel eluting with 0-20% ethyl acetate in hexane gave the title compound as a yellow oil (3.86 g, 10.6 mmol).

Workup

  1. additionwas added portionwise
  2. customgave a dark red colour change
  3. temperatureThe reaction mixture was heated at 100° C. for 20 hours under argon
  4. customcompletion of the reaction
  5. temperatureThe reaction mixture was cooled to room temperature
  6. custompartitioned between 2N Hydrochloric acid (75 ml) and ethyl acetate (75 ml)
  7. extractionThe aqueous layer was extracted with ethyl acetate (2×75 ml)
  8. customthe combined organic fractions were evaporated to a yellow oil
  9. customPurification by chromatography on silica gel eluting with 0-20% ethyl acetate in hexane

Sources & evidence

ORD record
ord-bfd5c8924f3e4c34b9d0615bc33b58ed
Source dataset
uspto-grants-2012_08
Patent number
US08252833B2

Reaction notes

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