Potassium Carbonate → (R)-5-(Oxiran-2-ylmethoxy)quinoline

Temperatur

50 °C

A mixture of 5-hydroxyquinoline (5.60 g, 38.6 mmol), R-glycidyl nosylate (10.0 g, 38.6 mmol), powdered potassium carbonate (11.7 g, 84.9 mmol), and N,N-dimethylformamide (100 mL) was stirred at ambient temperature until HPLC analysis (40% acetonitrile/60% of a 0.5% aqueous ammonium acetate solution, 1 mL/min, wavelength=230 nm, Zorbax RX-C8 25 cm×4.6 mm column) indicated complete disappearance of glycidyl nosylate (approximately 6 hours). The reaction mixture was filtered through paper and the filter cake was washed with 200 mL of a 3:1 mixture of MTBE and methylene chloride. The filtrate was washed with 200 mL of water and the aqueous layer was extracted four times with 100 mL of 3:1 MTBE/methylene chloride. The combined organic layers were dried over 30 grams of magnesium sulfate and the dried solution was then stirred with 50 grams of basic alumina for 30 minutes. The alumina was removed by filtration and the filter cake was washed with 200 mL of 3:1 MTBE/methylene chloride. The filtrate was concentrated to a volume of 100 mL, 300 mL of MTBE were added, and the solution was again concentrated to 80 mL. After heating to 50° C., the solution was treated with 160 mL of heptane dropwise over 15 minutes, allowed to cool to 40° C., and seeded, causing the formation of a crystalline precipitate. The mixture was stirred for two hours at ambient temperature and then at 0-5° C. for an additional 2 hours. The crystals were filtered, washed with cold heptane, and dried to provide 5.68 g (73.2%) of (2R)-1-(5-quinolinyloxy)-2,3-epoxypropane as white needles.

1. filtrationThe reaction mixture was filtered through paper
2. washthe filter cake was washed with 200 mL of a 3:1 mixture of MTBE and methylene chloride
3. washThe filtrate was washed with 200 mL of water
4. extractionthe aqueous layer was extracted four times with 100 mL of 3:1 MTBE/methylene chloride
5. dry with materialThe combined organic layers were dried over 30 grams of magnesium sulfate
6. customThe alumina was removed by filtration
7. washthe filter cake was washed with 200 mL of 3:1 MTBE/methylene chloride
8. concentrationThe filtrate was concentrated to a volume of 100 mL, 300 mL of MTBE
9. additionwere added
10. concentrationthe solution was again concentrated to 80 mL
11. additionthe solution was treated with 160 mL of heptane dropwise over 15 minutes
12. temperatureto cool to 40° C.
13. stirringThe mixture was stirred for two hours at ambient temperature
14. waitat 0-5° C. for an additional 2 hours
15. filtrationThe crystals were filtered
16. washwashed with cold heptane
17. customdried

ORD-Eintrag

ord-37c429bf3cd24e9c905d335c3dcbe732

Quelldatensatz

uspto-grants-2003_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06570016B1