Ethanol → 2-(2,5-Difluoro-4-nitro-phenyl)-4-methyl-pentanoic acid ethyl ester

HRID 385321Notes

Reaction equation

HRID 385321 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[C:5]([F:11])=[CH:4][C:3]=1[CH:12]([CH2:16][CH:17]([CH3:19])[CH3:18])[C:13]([OH:15])=[O:14].OS(O)(=O)=O.[CH3:25][CH2:26]O>>[CH2:25]([O:14][C:13](=[O:15])[CH:12]([C:3]1[CH:4]=[C:5]([F:11])[C:6]([N+:8]([O-:10])=[O:9])=[CH:7][C:2]=1[F:1])[CH2:16][CH:17]([CH3:19])[CH3:18])[CH3:26]

Participants

4

Reactant 3

HCID 702EthanolHCID 1118Sulfuric AcidHCID 579955592-(2,5-Difluoro-4-nitro-phenyl)-4-methyl-pentanoic acid

Product 1

HCID 579956072-(2,5-Difluoro-4-nitro-phenyl)-4-methyl-pentanoic acid ethyl ester

Procedure

2-(2,5-difluoro-4-nitro-phenyl)-4-methyl-pentanoic acid (29.0 g, 0.11 mol) was dissolved in EtOH (200 mL) and H2SO4 (96%) 10 mL added. The reaction mixture was refluxed for 3 h and the solvent evaporated to an oil which was dissolved in EtOAc. Water (150 mL) added and the reaction mixture was extracted with EtOAc (3×100 mL). Organic phases washed with saturated NaHCO3 (50 mL), water (100 mL) and brine (100 mL) then dried under MgSO4. The evaporation of solvent under reduced pressure gave 2-(2,5-difluoro-4-nitro-phenyl)-4-methyl-pentanoic acid ethyl ester as yellow oil 32.0 g, (97%), which was used for the next step without purification. 1H NMR (300 MHz, CDCl3/TMS): δ 7.81 (dd, J=8.8, 6.2 Hz, 1H), 7.41 (dd, J=11.1, 5.6 Hz, 1H), 4.23-4.05 (m, 3H), 2.04-1.94 (m, 1H), 1.71-1.62 (m, 1H), 1.51-1.42 (m, 1H), 1.25 (t, J=7.1 Hz, 3H), 0.95-0.92 (m, 6H); 13C NMR (75 MHz, CDCl3/TMS): δ 171.6, 155.0 (d, 1JCF=246.0 Hz), 151.5 (d, 1JCF=261.3 Hz), 145.5, 135.7, 118.8 (dd, 2JCF=24.0, 3JCF=4.0 Hz), 113.0 (d, 2JCF=20.0 Hz), 61.6, 41.8, 26.1, 22.5, 22.0, 14.1.

Workup

  1. temperatureThe reaction mixture was refluxed for 3 h
  2. customthe solvent evaporated to an oil which
  3. dissolutionwas dissolved in EtOAc
  4. additionWater (150 mL) added
  5. extractionthe reaction mixture was extracted with EtOAc (3×100 mL)
  6. washOrganic phases washed with saturated NaHCO3 (50 mL), water (100 mL) and brine (100 mL)
  7. customthen dried under MgSO4
  8. customThe evaporation of solvent under reduced pressure

Sources & evidence

ORD record
ord-8cbc8df4de614d99b560cd7dd56ee12a
Source dataset
uspto-grants-2013_02
Patent number
US08367863B2

Reaction notes

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