Hexane → 1-Bromo-3-iodo-5-methoxybenzene

Temperature

-5 °C

A 1.6 M solution of n-butyllithium in hexane (5.65 mL, 9.04 mmol) was dissolved in dry toluene (50 mL) under dry argon and cooled to −5° C. Then a 2M solution of n-butylmagnesium chloride (2.26 mL, 4.52 mmol) was added slowly with the temperature held below 0° C. over a period of 15 min. Stirring was continued for 45 min at −5° C., followed by drop wise addition of a solution of 1,3-dibromo-5-methoxy-benzene (3.00 g, 11.3 mmol) in toluene (30 mL) with the temperature held below 0° C. The mixture was stirred for 45 min at −5° C. A solution of iodine chloride (1.83 g, 11.3 mmol) in methylene chloride (20 mL) was added in the described manner and stirring continued for additional 20 min at −5° C. The mixture was warmed to room temperature. Water (50 mL) and toluene (50 mL) were added and the layers were separated. The organic layer was washed with a saturated aqueous solution of Na2S2O3 (2×30 mL), water and brine (30 mL). The organic layer was dried (MgSO4) and concentrated to give the crude product which was purified by flash chromatography on silica gel (100 g, AcOEt/heptane 1:9). 1-Bromo-3-iodo-5-methoxy-benzene (2.12 g, 60%) was obtained as a yellow oil, which crystallized quickly upon standing.

1. waitwas continued for 45 min at −5° C.
2. customheld below 0° C
3. stirringThe mixture was stirred for 45 min at −5° C
4. stirringstirring
5. waitcontinued for additional 20 min at −5° C
6. temperatureThe mixture was warmed to room temperature
7. customthe layers were separated
8. washThe organic layer was washed with a saturated aqueous solution of Na2S2O3 (2×30 mL), water and brine (30 mL)
9. dry with materialThe organic layer was dried (MgSO4)
10. concentrationconcentrated
11. customto give the crude product which
12. customwas purified by flash chromatography on silica gel (100 g, AcOEt/heptane 1:9)

ORD record

ord-ad593bde0fd14ee0b8927e3856b5335d

Source dataset

uspto-grants-2009_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07504401B2