Sodium hydride → HCID 22345402, compound

A solution of 2-bromo-4,6-di-tert-butyl-phenol (18.58 g, 65 mmol) in DMF (200 mL) was added to a stirred slurry of sodium hydride in anhydrous DMF (500 mL) precooled to −7° C. over 15 min. The resulting reaction mixture was stirred at <0° C. for 0.5 h. n-Propyl iodide was added and stirring of the olive green reaction mixture was continued for 18 h. after removal of the ice bath. The reaction was quenched with de-ionized water (2.5 L), 1 M HCl (250 mL) and 5% LiCl solution (250 mL). The resulting mixture was extracted with ethyl acetate (2×250 mL). Sodium chloride (q.s. to saturation) was added to facilitate the separation. The aqueous layer was extracted with hexane (200 mL). The combined organic layers were washed with 5% LiCl (2×200 mL) dried (MgSO4) and filtered. The solvent was removed under vacuum to give a viscous oil which was a 2:1 ration of product to DMF. The residue was dissolved in hexane (100 mL) and the solution was washed with 5% LiCl solution (3×30 mL). The hexane solution was dried (MgSO4), filtered, and the hexane was removed under vacuum to give a light brown oil which crystallized on standing to give a tan solid (21.23 g, 99%). The product may be purified by sublimation at 150° C. at 0.5 torr to give a light yellow solid. NMR (250 Mz, CDCl3): δ 7.32 (d, 1H, J=2.4 Hz), 7.20 (d, 1H, J=2.4), 3.92 (t, 2H, J=6.8), 1.82 (sex, 2H), 1.00 (t, 3H, J=7.4). MS [EI+] 326, 328 (M+H)+.

1. customThe resulting reaction mixture
2. additionwas added
3. waitwas continued for 18 h.
4. customafter removal of the ice bath
5. customThe reaction was quenched with de-ionized water (2.5 L), 1 M HCl (250 mL) and 5% LiCl solution (250 mL)
6. extractionThe resulting mixture was extracted with ethyl acetate (2×250 mL)
7. additionSodium chloride (q.s. to saturation) was added
8. customthe separation
9. extractionThe aqueous layer was extracted with hexane (200 mL)
10. washThe combined organic layers were washed with 5% LiCl (2×200 mL)
11. dry with materialdried (MgSO4)
12. filtrationfiltered
13. customThe solvent was removed under vacuum
14. customto give a viscous oil which
15. washthe solution was washed with 5% LiCl solution (3×30 mL)
16. dry with materialThe hexane solution was dried (MgSO4)
17. filtrationfiltered
18. customthe hexane was removed under vacuum
19. customto give a light brown oil which
20. customcrystallized

ORD record

ord-7e26ce4e3fe343d79f6b940d5294da99

Source dataset

uspto-grants-2008_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07348359B2