Iodine → HCID 86690451, compound

Temperature

-78 °C

A solution of 1-bromo-3,5-dimethoxybenzene (20 g, 92.1 mmol) in THF (100 ml) was added to a flask (500 ml) with magnesium (2.5 g, 103 mmol), I2 (20 mg) and THF (50 ml) and refluxed for 2 h. The resulting light brown solution was transferred to another flask (500 ml) and was cooled to −78° C. Diethyl phosphorochloridate (17.8 g, 103 mmol) in THF (80 ml) was added at −78° C. within 1 h. The mixture was stirred at −78° C. for 1 h, then slowly warmed up to RT and stirred at RT overnight. Brine (20%, 200 ml) was added to the mixture and it was stirred for 30 min. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (200 ml×1) and CH2Cl2 (100 ml×1). The combined organic layer was washed with brine (300 ml×2) and dried over MgSO4. It was filtered and the solvent was removed. The residues were purified with silica gel pad (eluent: CH2Cl2 to removed impurities, then CH2Cl2/THF=10/1 to wash out the product). The pure product was obtained as pale a yellow oil after the solvent was removed (20.2 g, 80% yield). 1H NMR (300 Mhz, CD2Cl2) δ: 6.90 (dd, J1=2.1 Hz, J2=14.7 Hz, 2H), 6.63 (d, J=2.1 Hz, 1H), 4.05 (quart, J=6.9 Hz, 4H), 3.83 (s, 6H), 1.31 (t, J=6.9 Hz, 6H). 31P NMR (121.5 MHz, CD2Cl2) δ: 19.10.

1. temperaturerefluxed for 2 h
2. customThe resulting light brown solution was transferred to another flask
3. temperatureslowly warmed up to RT
4. stirringstirred at RT overnight
5. stirringwas stirred for 30 min
6. customThe organic layer was separated
7. extractionthe aqueous layer was extracted with ethyl acetate (200 ml×1) and CH2Cl2 (100 ml×1)
8. washThe combined organic layer was washed with brine (300 ml×2)
9. dry with materialdried over MgSO4
10. filtrationIt was filtered
11. customthe solvent was removed
12. customThe residues were purified with silica gel pad (eluent
13. customCH2Cl2 to removed impurities
14. washCH2Cl2/THF=10/1 to wash out the product)
15. customThe pure product was obtained as pale a yellow oil after the solvent
16. customwas removed (20.2 g, 80% yield)

ORD record

ord-4590e3a9fcf74033b30d4aed4142df02

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09062085B2