Sulfuric Acid → (5S)-5-(3-methyl-1,2-oxazol-5-yl)pyrrolidin-2-one

To a cooled (0°-5° C.) solution of acetone oxime (11.74 g, 160.8 mmol)in THF (200 mL) was slowly added n-butyl lithium (128.6 mL, 2.5M, 321.6 mmol)in hexanes. After being stirred at 0°-5° C. for one hour, a solution of pyroglutamic methyl ester (10.0 g, ~69.9 mmol, the product of step 13a)in THF (50 mL) was added. After stirring for 4 hr, the solution was allowed to slowly warm up to room temperature, and the stirring was continued for 16 hr. Sulfuric acid (35 g, 98%) was slowly added with cooling, followed by the addition of water (35 mL). The resulting mixture was refluxed for one hour. The organic layer was decanted and the slurry was washed with ethyl acetate (5×50 mL). To the mixture was added ethyl acetate (400 mL) and sodium carbonate until basic. Again, the organic layer was decanted and the slurry was washed with ethyl acetate (4×20 mL). The combined organics were then dried over magnesium sulfate. Evaporation of the solvents gave the title product (5.33 g, 46%), which was taken directly to the next step. HPLC (analytical Chiralark AD column) analysis indicated >99.6% ee.

1. stirringAfter stirring for 4 hr
2. waitthe stirring was continued for 16 hr
3. temperaturewith cooling
4. temperatureThe resulting mixture was refluxed for one hour
5. customThe organic layer was decanted
6. washthe slurry was washed with ethyl acetate (5×50 mL)
7. additionTo the mixture was added ethyl acetate (400 mL) and sodium carbonate until basic
8. customAgain, the organic layer was decanted
9. washthe slurry was washed with ethyl acetate (4×20 mL)
10. dry with materialThe combined organics were then dried over magnesium sulfate
11. customEvaporation of the solvents

ORD record

ord-fd827c2df4e84318bfc0d200deab4a88

Source dataset

uspto-grants-1996_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05508418