Methyl iodide → 3-Bromo-2-methoxy-5-methylthiophene

Temperature

-78 °C

n-Butyl lithium (2.0M in pentane, 0.97 mL, 1.93 mmol) was added to a stirred solution of 3,5-dibromo-2-methoxythiophene (Step A, 500 mg, 1.84 mmol) in THF (5 mL) at −78° C. under an atmosphere of N2. The reaction stirred at −78° C. for 1 h prior to addition of methyl iodide (114 μL, 1.84 mmol). The reaction was allowed to warm to room temperature and stirred for 20 h. The solvent was removed under reduced pressure and the residue was partitioned between EtOAc (15 mL0 and H2O (15 mL). The aqueous layer was re-extracted with ether (2×15 mL) and the combined organic layers were washed with H2O (15 mL) and brine (15 mL), dried (MgSO4), filtered and concentrated in vacuo. The crude product was purified by flash silica gel chromatography (hexanes) to afford 3-bromo-2-methoxy-5-methylthiophene as a yellow oil. 1H NMR (CDCl3, 500 MHz): δ 6.44 (s, 1 H), 3.95 (s, 3 H), 2.41 (s, 3 H).

1. temperatureto warm to room temperature
2. stirringstirred for 20 h
3. customThe solvent was removed under reduced pressure
4. customthe residue was partitioned between EtOAc (15 mL0 and H2O (15 mL)
5. extractionThe aqueous layer was re-extracted with ether (2×15 mL)
6. washthe combined organic layers were washed with H2O (15 mL) and brine (15 mL)
7. dry with materialdried (MgSO4)
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe crude product was purified by flash silica gel chromatography (hexanes)

ORD record

ord-f93b7d36c9e44752a1ad49346bb41804

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08735435B2