Potassium Carbonate → 5-(4-(Difluoromethyl)phenyl)-4-methyloxazole

HRID 1672569Notes

Reaction equation

HRID 1672569 reaction equation
[F:1][CH:2]([F:11])[C:3]1[CH:10]=[CH:9][C:6]([CH:7]=[O:8])=[CH:5][CH:4]=1.[N+:12]([CH:14](S(C1C=CC(C)=CC=1)(=O)=O)[CH3:15])#[C-:13].C([O-])([O-])=O.[K+].[K+]>CO>[F:1][CH:2]([F:11])[C:3]1[CH:4]=[CH:5][C:6]([C:7]2[O:8][CH:13]=[N:12][C:14]=2[CH3:15])=[CH:9][CH:10]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 110528851-(1-Isocyanoethanesulfonyl)-4-methylbenzeneHCID 117688064-(Difluoromethyl)benzaldehyde

Product 1

HCID 666966055-(4-(Difluoromethyl)phenyl)-4-methyloxazoleYield 89%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of Example 38C (3.68 g, 23.6 mmol), 1-(1-isocyanoethylsulfonyl)-4-methylbenzene (4.93 g, 23.6 mmol), and K2CO3 (3.26 g, 23.6 mmol) in MeOH (110 mL) was heated to reflux. After 1 hr the reaction mixture was cooled to ambient temperature and the volatiles evaporated at reduced pressure. The residue was partitioned between Et2O and H2O. The separated aqueous phase was extracted with Et2O, and the combined organic extract was washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. Flash chromatography (Analogix® Intelliflash 280™; 5% to 25% EtOAc/hexanes eluant; SF40-150 g column) afforded 4.39 g (89%) of the title compound as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 8.40 (s, 1H), 7.80-7.73 (m, 2H), 7.69 (d, J=8.6, 2H), 7.09 (t, J=55.3, 1H), 2.40 (s, 3H). MS (DCI+) m/z 210 (M+H).

Workup

  1. customthe volatiles evaporated at reduced pressure
  2. customThe residue was partitioned between Et2O and H2O
  3. extractionThe separated aqueous phase was extracted with Et2O
  4. extractionthe combined organic extract
  5. washwas washed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1e224d71eefd46ef885bf9381640cd1c
Source dataset
uspto-grants-2011_08
Patent number
US07998993B2

Reaction notes

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