Tetrahydrofuran → 2-(2-iminooxazol-3(2H)-yl)-1-(2,4,5-trifluorophenyl)ethanone hydrobromide

HRID 1929971Notes

Reaction equation

HRID 1929971 reaction equation
[Br:1][CH2:2][C:3]([C:5]1[CH:10]=[C:9]([F:11])[C:8]([F:12])=[CH:7][C:6]=1[F:13])=[O:4].[O:14]1[CH:18]=[CH:17][N:16]=[C:15]1[NH2:19].C1COCC1>C(#N)C>[BrH:1].[NH:19]=[C:15]1[N:16]([CH2:2][C:3]([C:5]2[CH:10]=[C:9]([F:11])[C:8]([F:12])=[CH:7][C:6]=2[F:13])=[O:4])[CH:17]=[CH:18][O:14]1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 5585212-AminooxazoleHCID 27831812,4,5-Trifluorophenacyl bromide

Product 1

HCID 685087792-(2-iminooxazol-3(2H)-yl)-1-(2,4,5-trifluorophenyl)ethanone hydrobromideYield 79%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
23 °C

Procedure

A round bottom flask was charged with 2-bromo-1-(2,4,5-trifluorophenyl)ethanone (50.0 g, 198 mmol), oxazole-2-amine (GL Synthesis, 11.1 g, 132 mmol), THF (200 mL), and ACN (330 mL). The resulting mixture was stirred at about 23° C. for about 20 h. The suspension was cooled to about −10° C. for about 15 min and the solid was collected by vacuum filtration, washed with additional ACN (150 mL), and dried under vacuum to give 2-(2-iminooxazol-3(2H)-yl)-1-(2,4,5-trifluorophenyl)ethanone hydrobromide (35.1 g, 79%) as a white solid. A portion of this material (20.0 g, 59.3 mmol) was suspended in toluene (140 mL) and the suspension was cooled to about 0° C. To the flask was added a 1.0 M solution of TiCl4 in toluene (154 mL) over about 30 min. The mixture was stirred at about 0° C. for about 30 min and was then heated to about 100° C. for about 3 h. The mixture was cooled to ambient temperature, the toluene was decanted off, and ice was added with stirring to the remaining residue. The mixture was adjusted to about pH 8 with the addition of solid Na2CO3, followed by the addition of EtOAc. The mixture was stirred for about 1 h and then passed through a pad of Celite®. The layers were separated and the organic solution was dried over MgSO4, filtered, and concentrated to dryness under reduced pressure to give the title compound as a white solid (11.7 g, 83%): LC/MS (Table 1, Method b) Rt=2.11 min; MS m/z 239.1 (M+H)+.

Workup

  1. temperatureThe suspension was cooled to about −10° C. for about 15 min
  2. filtrationthe solid was collected by vacuum filtration
  3. washwashed with additional ACN (150 mL)
  4. customdried under vacuum

Sources & evidence

ORD record
ord-cdf89c0ffba349abb852c36153379ce6
Source dataset
uspto-grants-2012_05
Patent number
US08188083B2

Reaction notes

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