Methyl iodide → 1-Bromo-5-ethyl-2,4-dimethoxybenzene

A solution of tetrabutyl ammonium tribromide (15.4 g, 31.8 mmol) in CHCl3 (100 mL) was added to a stirred solution of 4-ethyl resorcinol (4 g, 29 mmol) dissolved in CHCl3 (50 mL). The reaction mixture was stirred for 2 hours and then quenched with 5% solution of sodium thiosulfate (30 mL). The biphasic mixture was stirred for 30 mins and then the layers were separated. The organic layer was washed with 1 N HCl, brine, dried over Na2SO4 and concentrated to yellow oil. The oil was dissolved in DMF (60 mL) and treated with K2CO3 (12.7 g, 92 mmol), followed by methyl iodide (2.9 mL, 46 mmol). The mixture was stirred for 15 hours and then partitioned between H2O and EtOAc. The organic layers were washed with 1 N HCl, brine, dried over Na2SO4 and concentrated to a dark red oil. Purification by flash column chromatography (0% to 10% EtOAc in hexanes) gave the product as a yellow oil (2.8 g, 39%). 1H NMR (400 MHz, CDCl3): δ 1.15 (t, J=7.6 Hz, 3 H), 2.54 (q, J=7.6 Hz, 2 H), 3.83 (s, 3 H), 3.89 (s, 3 H), 6.46 (s, 1 H), 7.26 (s, 1 H).

1. customquenched with 5% solution of sodium thiosulfate (30 mL)
2. stirringThe biphasic mixture was stirred for 30 mins
3. customthe layers were separated
4. washThe organic layer was washed with 1 N HCl, brine
5. dry with materialdried over Na2SO4
6. concentrationconcentrated to yellow oil
7. dissolutionThe oil was dissolved in DMF (60 mL)
8. stirringThe mixture was stirred for 15 hours
9. custompartitioned between H2O and EtOAc
10. washThe organic layers were washed with 1 N HCl, brine
11. dry with materialdried over Na2SO4
12. concentrationconcentrated to a dark red oil
13. customPurification by flash column chromatography (0% to 10% EtOAc in hexanes)

ORD record

ord-1326954752b344b8af64d271a0bc5d92

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08268835B2