2-(3-Fluoro-4-nitro-phenyl)-2-isobutyl-malonic acid Diethyl Ester → 2-(3-Fluoro-4-nitro-phenyl)-4-methyl-pentanoic acid

HRID 1183614Notes

Reaction equation

HRID 1183614 reaction equation
C([O:3][C:4](=[O:25])[C:5]([C:15]1[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[C:17]([F:24])[CH:16]=1)([CH2:11][CH:12]([CH3:14])[CH3:13])C(OCC)=O)C>CC(O)=O.O.OS(O)(=O)=O>[F:24][C:17]1[CH:16]=[C:15]([CH:5]([CH2:11][CH:12]([CH3:14])[CH3:13])[C:4]([OH:25])=[O:3])[CH:20]=[CH:19][C:18]=1[N+:21]([O-:23])=[O:22]

Participants

3

Reactant 1

HCID 579956132-(3-Fluoro-4-nitro-phenyl)-2-isobutyl-malonic acid Diethyl Ester

Product 1

HCID 579956222-(3-Fluoro-4-nitro-phenyl)-4-methyl-pentanoic acid

Reagents, catalysts & solvents 1

HCID 86597087Acetic acid sulfuric acid waterSolvent

Procedure

2-(3-Fluoro-4-nitro-phenyl)-2-isobutyl-malonic acid diethyl ester (92.0 g, 0.26 mol) was dissolved in AcOH/H2O/H2SO4 (96%) (500 mL/200 mL/70 mL) and the reaction mixture was refluxed for 24 h. After cooling and evaporation, water (300 mL) was added. The reaction mixture was extracted with EtOAc (3×100 mL). The combined organic phases were washed with water (3×100 mL), brine (100 mL) and dried (MgSO4). The evaporation of solvent under reduced pressure gave a brown oil (61 g, quantitative), which was used for the next step without purification. 1H NMR (300 MHz, CDCl3/TMS): δ 8.07-8.01 (m, 1H), 7.33-7.26 (m, 2H), 3.79-3.73 (m, 1H), 2.05-1.95 (m, 1H), 1.76-1.66 (m, 1H), 1.52-1.43 (m, 1H), 0.95-0.92 (m, 6H); 13C NMR (75 MHz, CDCl3/TMS): δ 178.3, 156.0 (d, 1JCF=232.5 Hz), 147.0, 136.0, 126.2, 124.3, 118.1 (d, 2JCF=30 Hz), 49.3, 42.0, 25.8, 22.4, 22.0.

Workup

  1. temperaturethe reaction mixture was refluxed for 24 h
  2. temperatureAfter cooling
  3. customevaporation, water (300 mL)
  4. additionwas added
  5. extractionThe reaction mixture was extracted with EtOAc (3×100 mL)
  6. washThe combined organic phases were washed with water (3×100 mL), brine (100 mL)
  7. dry with materialdried (MgSO4)
  8. customThe evaporation of solvent under reduced pressure
  9. customgave a brown oil (61 g, quantitative), which
  10. customwas used for the next step without purification

Sources & evidence

ORD record
ord-b2b675dee6564558b5c7866130b4fe9b
Source dataset
uspto-grants-2014_03
Patent number
US08664249B2

Reaction notes

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