Potassium Carbonate → 4-Ethyl-5-(2-fluoro-4-(trifluoromethyl)phenyl)oxazole

HRID 1672579Notes

Reaction equation

HRID 1672579 reaction equation
[N+:1]([CH:3](S(C1C=CC(C)=CC=1)(=O)=O)[CH2:4][CH3:5])#[C-:2].[F:16][C:17]1[CH:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[CH:21][C:18]=1[CH:19]=[O:20].C([O-])([O-])=O.[K+].[K+]>CO>[CH2:4]([C:3]1[N:1]=[CH:2][O:20][C:19]=1[C:18]1[CH:21]=[CH:22][C:23]([C:25]([F:26])([F:27])[F:28])=[CH:24][C:17]=1[F:16])[CH3:5]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 5229292-Fluoro-4-(trifluoromethyl)benzaldehydeHCID 204671891-Ethyl-1-tosylmethyl isocyanide

Product 1

HCID 666966994-Ethyl-5-(2-fluoro-4-(trifluoromethyl)phenyl)oxazoleYield 50%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 1-(1-isocyanopropylsulfonyl)-4-methylbenzene (1.55 g, 6.94 mmol), 2-fluoro-4-(trifluoromethyl)benzaldehyde (0.95 mL, 6.9 mmol), and K2CO3 (1.15 g, 8.33 mmol) in MeOH (35 mL) was heated at reflux overnight. The reaction was cooled to ambient temperature and the volatiles evaporated at reduced pressure. The residue was diluted with water and the product extracted with EtOAc. The combined organic extract was washed with water and brine, dried (Na2SO4), filtered, and concentrated in vacuo. The crude product was chromatographed on silica gel (Analogix® 40×150 column, 10%-70% EtOAc/hexanes) to yield 0.89 g (50%) of the title compound. 1H NMR (300 MHz, CDCl3) δ 7.95 (s, 1H), 7.67-7.60 (m, 1H), 7.53-7.48 (m, 1H), 7.47-7.42 (m, 1H), 2.67 (qd, J=7.5, 1.6, 2H), 1.29 (t, J=7.5, 3H). MS (DCI+) m/z 260 (M+H).

Workup

  1. temperaturewas heated
  2. temperatureat reflux overnight
  3. customthe volatiles evaporated at reduced pressure
  4. additionThe residue was diluted with water
  5. extractionthe product extracted with EtOAc
  6. extractionThe combined organic extract
  7. washwas washed with water and brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude product was chromatographed on silica gel (Analogix® 40×150 column, 10%-70% EtOAc/hexanes)

Sources & evidence

ORD record
ord-ad43de420ecb481f83218d29b909447f
Source dataset
uspto-grants-2011_08
Patent number
US07998993B2

Reaction notes

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