Trifluoroacetic acid → 2-Benzoxazolinone, 5-methoxy-

Temperature

70 °C

2-amino-4-(methyloxy)phenol, HCl salt (1.0 g, 5.7 mmol) was dissolved in 20 mL of anhydrous tetrahydrofuran under argon. The mixture was heated to reflux (70° C.) and then 1,1′-carbonyldiimidazole (1.2 g, 7.4 mmol) was slowly added in small portions over a one hour period. After the addition was complete, the reaction continued to reflux for another 2.5 hours, before it was determined to be complete by LCMS (two Aquasil C18, 20×1 mm columns were run in sequence, 4 minutes at 0.1 mL/min, 1-99% CH3CN/H2O with 0.018% trifluoroacetic acid, ES) Rt=1.0 min and m/e 166 [M+1]+. The mixture was allowed to cool to room temperature before all volatiles were removed by rotary evaporation. The crude residue was dissolved in 100 mL of ethyl ether and washed with water (3×30 mL) and brine (3×30 mL). The organic layer was dried over Na2SO4, filtered and concentrated to give 5-(methyloxy)-1,3-benzoxazol-2(3H)-one (0.78 g, 4.7 mmol, 82%) as an orange amorphous solid. MS (ES) m/e 166 [M+H]+.

1. temperatureThe mixture was heated
2. additionAfter the addition
3. temperatureto reflux for another 2.5 hours, before it
4. temperatureto cool to room temperature before all volatiles
5. customwere removed by rotary evaporation
6. dissolutionThe crude residue was dissolved in 100 mL of ethyl ether
7. washwashed with water (3×30 mL) and brine (3×30 mL)
8. dry with materialThe organic layer was dried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated

ORD record

ord-22c9af82375e4ced967db05ab1c4d562

Source dataset

uspto-grants-2010_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07749998B2