Ethanol → 4-Methyl-2-(4-nitro-3-trifluoromethyl-phenyl)-pentanoic acid ethyl ester

HRID 1183607Notes

Reaction equation

HRID 1183607 reaction equation
[CH3:1][CH:2]([CH3:21])[CH2:3][CH:4]([C:8]1[CH:13]=[CH:12][C:11]([N+:14]([O-:16])=[O:15])=[C:10]([C:17]([F:20])([F:19])[F:18])[CH:9]=1)[C:5]([OH:7])=[O:6].S(=O)(=O)(O)O.[CH2:27](O)[CH3:28]>>[CH2:27]([O:6][C:5](=[O:7])[CH:4]([C:8]1[CH:13]=[CH:12][C:11]([N+:14]([O-:16])=[O:15])=[C:10]([C:17]([F:18])([F:19])[F:20])[CH:9]=1)[CH2:3][CH:2]([CH3:21])[CH3:1])[CH3:28]

Participants

4

Reactant 3

HCID 702EthanolHCID 1118Sulfuric AcidHCID 579956164-Methyl-2-(4-nitro-3-trifluoromethyl-phenyl)-pentanoic acid

Product 1

HCID 579955184-Methyl-2-(4-nitro-3-trifluoromethyl-phenyl)-pentanoic acid ethyl esterYield 83%

Procedure

To a solution of 4-methyl-2-(4-nitro-3-trifluoromethyl-phenyl)-pentanoic acid (42.3 g, 139 mmol) in absolute ethanol (300 mL) was added concentrated sulfuric acid (95-98%, 9.0 mL) and the solution was heated at reflux overnight. The reaction mixture was concentrated under reduced pressure; the residue was treated with a solution of sodium carbonate (5%, 300 mL) and the mixture was extracted with ethyl acetate (300 mL). The organic layer was washed with brine (300 mL), dried over sodium sulfate, and concentrated under reduced pressure. Purification by silica-gel flash chromatography eluting with heptane/EtOAc (10:1) gave 4-methyl-2-(4-nitro-3-trifluoromethyl-phenyl)-pentanoic acid ethyl ester (38.4 g, 83%) as a yellowish oil: 1H NMR (300 MHz, CDCl3): δ 7.90 (d, 1H, J=8.4 Hz), 7.82 (s, 1H), 7.74 (dd, 1H, J=8.4, 1.5 Hz), 4.18 (m, 2H), 3.83 (t, 1H, J=7.5 Hz), 2.06 (m, 1H), 1.70 (m, 1H), 1.50 (m, 1H), 1.27 (t, 3H, J=7.2 Hz), 0.97 (d, 3H, J=6.6 Hz), 0.96 (d, 3H, J=6.3 Hz); 13C NMR (75 MHz, CDCl3): δ 172.24, 146.83, 145.04, 132.40, 127.51 (q, J=5 Hz), 125.28, 123.80 (q, J=32 Hz), 121.78 (q, J=272 Hz), 61.45, 49.45, 42.65, 26.03, 22.41, 22.17, 14.10.

Workup

  1. temperaturethe solution was heated
  2. temperatureat reflux overnight
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. additionthe residue was treated with a solution of sodium carbonate (5%, 300 mL)
  5. extractionthe mixture was extracted with ethyl acetate (300 mL)
  6. washThe organic layer was washed with brine (300 mL)
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customPurification by silica-gel flash chromatography
  10. washeluting with heptane/EtOAc (10:1)

Sources & evidence

ORD record
ord-2f11f595d0834954bf15838c393bcb22
Source dataset
uspto-grants-2014_03
Patent number
US08664249B2

Reaction notes

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