Ethanol → Methyl (5-methyl-2-phenyl-1,3-oxazol-4-yl)acetate

HRID 2300586Notes

Reaction equation

Br[CH:2]([CH3:10])[C:3](=O)[CH2:4][C:5]([O:7][CH3:8])=[O:6].[C:11]([NH2:19])(=[O:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.P([O-])([O-])(O)=O.[Na+].[Na+].CCO>C1(C)C=CC=CC=1>[CH3:8][O:7][C:5](=[O:6])[CH2:4][C:3]1[N:19]=[C:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[O:18][C:2]=1[CH3:10]

Participants

Conditions

Temperature: 95 °C

Procedure

To a solution of 140 g (0.67 mol) of methyl 4-bromo-3-oxo-pentanoate in 300 mL of anhydrous toluene was added 210 g (1.73 mol) of benzamide, 132 g (0.93 mol) of sodium hydrogen phosphate, and ˜20 mL of EtOH. The suspension was stirred with heating to 95° C. for 24 h, then cooled to 0° C., filtered, and the solids washed with cyclohexane (2×100 mL) followed by 20% EtOAc in hexanes (200 mL). The combined filtrates were washed with 2×100 mL 10% KOH solution and brine (100 mL). The organics were dried (MgSO4), concentrated to a thin oil, and purified by chromatography on 1 kg of silica gel (230-400 mesh). Gradient elution of the column with 10% to 50% EtOAc in Hexanes gave 54 grams (35% yield) of the title compound as a pale yellow oil; 1H NMR (CDCl3, 400 MHz) δ8.0-7.98 (m, 2H), 7.43-7.40 (m, 3H), 3.73 (s, 3H), 3.59 (s, 2H), 2.37 (s, 3H); low resolution MS (ES+)m/e 232.4 (MH+); TLC Rf=0.64 (4/1 hexanes/EtOAc).

Workup

temperaturecooled to 0° C.
filtrationfiltered
washthe solids washed with cyclohexane (2×100 mL)
washThe combined filtrates were washed with 2×100 mL 10% KOH solution and brine (100 mL)
dry with materialThe organics were dried (MgSO4)
concentrationconcentrated to a thin oil
custompurified by chromatography on 1 kg of silica gel (230-400 mesh)
washGradient elution of the column with 10% to 50% EtOAc in Hexanes

Sources & evidence

ORD record: ord-855e530344284c1dbbfb0fcff88acef9
Source dataset: uspto-grants-2002_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06498174B1

Reaction notes

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