Sulfuric Acid → Methyl 4-aminophenylacetate hydrogensulfate

Temperature

50 °C

The 4-aminophenylacetamide used in this example was obtained according to patent literature WO 02/08247 A2 or WO 03/051909 A2. Procedure was as follows: Methanol (200 mL) was charged to 4-aminophenylacetic acid (Aldrich) (25 g, 0.165 mol). Sulfuric acid (18 mL concentrated, 0.648 mol) was added maintaining the temperature <20° C. The mixture was then refluxed for one hour and concentrated by distillation at atmospheric pressure until the volume of 140 mL. The mixture was then cooled to 50° C. and tert-buthyl methyl ether (300 mL) was added maintaining the temperature above 45° C. The mixture was gradually cooled to 0-5° C. and held at this temperature for 1 hour. The resultant crystalline product was isolated by filtration and washed with cold methanol:tert-butyl methyl ether (20 mL:55 mL) and cold tert-butyl methyl ether and then dried under vacuum to give methyl 4-aminophenylacetate hydrogensulfate (35.3 g, 80% yield).

1. customwas obtained
2. temperaturemaintaining the temperature <20° C
3. temperatureThe mixture was then refluxed for one hour
4. concentrationconcentrated by distillation at atmospheric pressure until the volume of 140 mL
5. additiontert-buthyl methyl ether (300 mL) was added
6. temperaturemaintaining the temperature above 45° C
7. temperatureThe mixture was gradually cooled to 0-5° C.
8. customThe resultant crystalline product was isolated by filtration
9. washwashed with cold methanol
10. dry with materialtert-butyl methyl ether (20 mL:55 mL) and cold tert-butyl methyl ether and then dried under vacuum

ORD record

ord-af354de492ca4915871b09f55db1b9e0

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08487130B2