Ammonia → 2-(5-Methyl-2-phenyl-oxazol-4-yl)-ethylammonium mesylate

Temperature

20 °C

A 1500 mL double jacketed stainless steel autoclave equipped with a mechanical stirring bar and a Pt-100 thermometer was charged under nitrogen with 100 g (355 mmol) of methanesulfonic acid 2-(5-methyl-2-phenyl-oxazol-4-yl)-ethyl ester and 900 mL of methanol. The autoclave was closed and ammonia (200 g, 11.74 mol) was transferred into the suspension at −20° C. to 20° C. while stirring and cooling. The mixture was then heated to 75° C.-80° C. and the pressure rose to 10 bar. The mixture was stirred for 2-3 h at this temperature and then cooled down to 20° C. The pressure was relieved and the clear solution was transferred with the aid of 100 mL of methanol to a 1000 mL double jacketed glass reactor equipped with a mechanical stirrer, a Pt-100 thermometer, a reflux condenser, a dropping funnel and a nitrogen inlet. The solvent was completely removed by distillation under vacuum. The resulting suspension was twice treated with 500 mL of methylenechloride that was subsequently completely removed by distillation under normal pressure. The residue was again treated with 500 mL of methylenechloride and the resulting suspension was cooled to 0° C. within 1 h and stirred for another 2 h at this temperature. The precipitate was filtered with suction, the filter cake was washed with 200 mL of methylenechloride and dried under vacuum (50° C., 50 mbar) to afford about 85.8 g (yield 78%, 96% (m/m) purity based on HPLC assay) of 2-(5-Methyl-2-phenyl-oxazol-4-yl)-ethylammonium mesylate as a colorless solid. The HPLC analysis was performed with an external standard of pure 2-(5-methyl-2-phenyl-oxazol-4-yl)-ethylammonium mesylate. Conditions for HPLC: Column XTerra RP8 Waters, 4.6×150 mm, 3.5 μm; UV detector 205 nm; solutions for gradient: water (A), acetonitrile (B), pH 6.5 buffer KH2PO4/K2HPO4 (C); flow 1.2 mL/min, 40° C.

1. customThe autoclave was closed
2. customwas transferred into the suspension at −20° C. to 20° C.
3. temperaturecooling
4. temperatureThe mixture was then heated to 75° C.-80° C.
5. stirringThe mixture was stirred for 2-3 h at this temperature
6. customequipped with a mechanical stirrer
7. customThe solvent was completely removed by distillation under vacuum
8. additionThe resulting suspension was twice treated with 500 mL of methylenechloride that
9. customwas subsequently completely removed by distillation under normal pressure
10. additionThe residue was again treated with 500 mL of methylenechloride
11. temperaturethe resulting suspension was cooled to 0° C. within 1 h
12. stirringstirred for another 2 h at this temperature
13. filtrationThe precipitate was filtered with suction
14. washthe filter cake was washed with 200 mL of methylenechloride
15. customdried under vacuum (50° C., 50 mbar)

ORD record

ord-f8724de6798f4cfe8acf1419e45b1f3b

Source dataset

uspto-grants-2010_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07772264B2