Water → 2-(4-Bromophenyl)-5-methyl-4-oxazoleacetic acid

HRID 348267Notes

Reaction equation

HRID 348267 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([CH3:16])=[C:11]([CH2:13][C:14]#N)[N:12]=2)=[CH:4][CH:3]=1.COCCO.[OH-:22].[K+].[OH2:24]>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([CH3:16])=[C:11]([CH2:13][C:14]([OH:24])=[O:22])[N:12]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 4

HCID 962WaterHCID 80192-MethoxyethanolHCID 14797Potassium HydroxideHCID 113694322-(2-(4-Bromophenyl)-5-methyloxazol-4-YL)acetonitrile

Product 1

HCID 113124822-(4-Bromophenyl)-5-methyl-4-oxazoleacetic acidYield 60%

Procedure

The crude 2-(4-bromophenyl-4-(cyanomethyl)-5-methyloxazole (assume 0.22 mol) was combined with 2-methoxyethanol (630 mL) and 85% solid KOH (74.6 g, 1.33 mol) in water (360 mL) was added to the reaction. The mixture was heated to reflux for 3 h, cooled, quenched with 2 M HCl (500 mL), and extracted with CH2Cl2. The organic layer was dried (MgSO4), and the solvent removed in vacuo, using toluene to azeotropically remove residual 2-methoxyethanol. The crude product (57.3 g) was recrystallized from toluene (450 mL) to give 39.8 g (60%) of 2-(4-bromophenyl)-5-methyl-4-oxazoleacetic acid as an off-white powder: Rf=0.23 in 10% MeOH/CH2Cl2; 1H NMR (500 MH, CDCl3) 9.00 (br s, 1H), 7.85–7.83 (m, 2H), 7.58–7.56 (m, 2H), 3.62 (s, 3H), 2.36 (s, 3H); 13C (125 MHz, CDCl3) 173.8, 159.0, 146.2, 132.0, 129.1, 127.6, 125.9, 124.7, 31.5, 10.2; IR (CHCl3) 2923, 1699, 1641, 1481, 1428, 1306, 1234, 1010, 829, 727 cm−1; UV (EtOH)max 288 nm (19626).

Workup

  1. additionwas added to the reaction
  2. temperatureThe mixture was heated
  3. temperatureto reflux for 3 h
  4. temperaturecooled
  5. customquenched with 2 M HCl (500 mL)
  6. extractionextracted with CH2Cl2
  7. dry with materialThe organic layer was dried (MgSO4)
  8. customthe solvent removed in vacuo
  9. customThe crude product (57.3 g) was recrystallized from toluene (450 mL)

Sources & evidence

ORD record
ord-245a41c9cc6c4230b8a5642221162fb4
Source dataset
uspto-grants-2007_02
Patent number
US07176224B2

Reaction notes

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