Hydrogen Peroxide → HCID 86690456, compound

1-Bromo-3,5-dimethoxybenzene (25.5 g, 117.5 mmol) in THF (150 mL) was added to a mixture of magnesium (3.14 g, 129.2 mmol) and iodine (120 mg) in THF (100 mL). The mixture was refluxed for 1 hour after the addition was completed. It was cooled to RT. The resulting light brown solution was transferred to another flask. It was cooled to −78° C. and chlorobis(3,5-di-tert-butyl-4-methoxyphenyl)phosphine (59.3 g, 117.4 mmol) in THF (100 mL) was added dropwise at −78° C. The resulting mixture was stirred at −78° C. for 0.5 h, then slowly warmed up to RT and stirred at RT for 1 hour. To the resulting mixture water (300 mL) was added, then H2O2 (17 mL, 30%) was added dropwise at 0° C. The mixture was stirred for 30 minutes. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (200 mL×2) and CH2Cl2 (200 mL×1). The combined organic layer was washed with brine (200 mL×2), NaHSO3 (200 mL×3) and dried over MgSO4. It was filtered and the solvent was removed. The viscous residue was dissolved in CH2Cl2 (30 mL) and ether (100 mL), then hexane (400 mL) added. The mixture was concentrated to 400 mL under reduced pressure and then seeded. The suspension was stirred for 1.5 hour and the resulting solid was collected by filtration and dried to give the product as a colorless solid (57 g). a second crop (13 g) was collected from the mother liquor. Yield=95.7%. 1H NMR (300 MHz, CDCl3) δ: 7.47 (d, J=12.6 Hz, 4H), 6.83 (dd, J1=12.6 Hz, J2=2.1 Hz, 2H), 6.60 (t, J=2.1 Hz, 2H), 3.78 (s, 6H), 3.68 (s, 6H), 1.35 (s, 36H). 31P NMR (121.5 MHz, CDCl3) δ: 32.9.

1. temperatureThe mixture was refluxed for 1 hour
2. additionafter the addition
3. customThe resulting light brown solution was transferred to another flask
4. temperatureIt was cooled to −78° C.
5. temperatureslowly warmed up to RT
6. stirringstirred at RT for 1 hour
7. stirringThe mixture was stirred for 30 minutes
8. customThe organic layer was separated
9. extractionthe aqueous layer was extracted with ethyl acetate (200 mL×2) and CH2Cl2 (200 mL×1)
10. washThe combined organic layer was washed with brine (200 mL×2), NaHSO3 (200 mL×3)
11. dry with materialdried over MgSO4
12. filtrationIt was filtered
13. customthe solvent was removed
14. dissolutionThe viscous residue was dissolved in CH2Cl2 (30 mL)
15. additionether (100 mL), then hexane (400 mL) added
16. concentrationThe mixture was concentrated to 400 mL under reduced pressure
17. stirringThe suspension was stirred for 1.5 hour
18. filtrationthe resulting solid was collected by filtration
19. customdried

ORD record

ord-db4d80fd9cc04e4389d146120b09b58c

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09062085B2