Sodium hydride → HCID 11089976, compound

Temperature

0 °C

Sodium hydride (1.3 g, 55 mmol) was suspended in THF (75 mL) and cooled to 0° C. The title compound of Example 1 (14.9 g, 55 mmol) was dissolved in THF (75 mL) and added dropwise to the suspension over 30 minutes. The resulting solution was stirred an additional 30 minutes after which time solid 5-methyl-2-phenyl-4-oxazolyl methyl chloride (10.0 g, 48 mmol) was added in portions over five minutes. The reaction mixture was refluxed for 48 hours, cooled to room temperature and concentrated in vacuo. The residue was dissolved in acetic acid (120 mL) and concentrated HCI (30 mL), and refluxed for five hours. The reaction mixture was cooled to room temperature and poured onto ice-water (300 mL). The aqueous solution was extracted twice with ethyl acetate (500 mL) and the organic extracts were combined and washed with brine (250 mL), dried (MgSO4) and concentrated in vacuo. Purification on silica gel, eluting with hexane/ethyl acetate (4/1), resulted in a crude solid which was further purified by recrystallization from hexane to afford the title compound (11.5 g, 65%) as white crystals. mp 80-81° C. 1HNMR (60 MHz, CDCl3): δ2.2 (s, 3H), 2.8 (m, 2H), 3.2 (m, 2H), 7.2-8.0 (m, 9H).

1. additionadded dropwise to the suspension over 30 minutes
2. additionwas added in portions over five minutes
3. temperatureThe reaction mixture was refluxed for 48 hours
4. temperaturecooled to room temperature
5. concentrationconcentrated in vacuo
6. dissolutionThe residue was dissolved in acetic acid (120 mL)
7. concentrationconcentrated HCI (30 mL)
8. temperaturerefluxed for five hours
9. temperatureThe reaction mixture was cooled to room temperature
10. additionpoured onto ice-water (300 mL)
11. extractionThe aqueous solution was extracted twice with ethyl acetate (500 mL)
12. washwashed with brine (250 mL)
13. dry with materialdried (MgSO4)
14. concentrationconcentrated in vacuo
15. customPurification on silica gel
16. washeluting with hexane/ethyl acetate (4/1)
17. customresulted in a crude solid which
18. customwas further purified by recrystallization from hexane

ORD record

ord-058066dc85dc4c8c8a76d64491fa762f

Source dataset

uspto-grants-2001_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06329408B1