Iodine → 2-Iodo-2',4',6'-triisopropyl-3,6-dimethoxybiphenyl

An oven-dried three-neck 500 mL round-bottom flask, which was equipped with a magnetic stir bar and charged with magnesium shavings (2.8 g, 116 mmol), was fitted with a reflux condenser, glass stopper, and rubber septum. The flask was purged with argon and then THF (100 mL) and 2,4,6-triisopropylbromobenzene (24.3 mL, 96 mmol) were added via syringe. The reaction mixture was heated to reflux and 1,2-dibromethane (40 uL) was added via syringe. The reaction was allowed to stir at reflux for 1.5 h and was then cooled to room temperature. A separate oven-dried 2 L round bottom flask, which was equipped with a magnetic stir bar and fitted with a septum, was purged with argon and then THF (500 mL) and 1,4-dimethoxy-2-fluorobenzene (7.49 g, 48 mmol) were added to the flask via syringe. The reaction mixture was cooled to −78° C. and n-BuLi (2.5 M in Hexane, 19.4 mL, 48.5 mmol) was added in a dropwise fashion over a 40 min period. The solution was stirred for 1 h and the Grignard reagent, which was prepared in the first reaction vessel, was added via cannula over a 30 min period and allowed to stir at −78° C. for 1 h. The reaction mixture was warmed to room temperature slowly where it was stirred for an additional 12 h. The mixture was then cooled to 0° C. and a solution of Iodine in THF (1 M, 96 mL, 96 mmol) was added via syringe over a 15 min period and then the dark red solution was warmed to room temperature and stirred for 1 h. The solvent was removed via a rotary evaporator, and the remaining dark brown oil was taken up in Et2O, washed with a saturated solution of sodium sulfite, and washed with brine. The organic layer was then dried over MgSO4, filtered, and the solvent was removed via rotary evaporator to give a yellow solid. The crude material was triturated with hexanes and filtered to give the desired product as an off-white solid (16.199 g, 72%, mp 189-191° C.). 1H NMR (300 MHz, CDCl3) δ: 7.07 (s, 2H), 6.90 (d, J=9.0 Hz, 1H), 6.81 (d, J=9.0 Hz, 1H), 3.90 (s, 3H), 3.67 (s, 3H), 2.98 (septet, J=7.0 Hz, 1H), 2.39 (septet, J=7.0 Hz, 2H), 1.33 (d, J=7.0 Hz, 6H), 1.20 (d, 7.0 Hz, 6H), 1.02 (d, J=7.0 Hz, 6H) ppm. 13C NMR (75 MHz, CDCl3) δ: 152.7, 152.5, 148.4, 145.9, 136.4, 136.1, 121.0, 110.3, 109.4, 96.6, 57.0, 55.8, 34.3, 31.1, 24.8, 24.3, 23.9 ppm. IR (neat, cm−1): 2957, 2865, 1567, 1460, 1428, 1257, 1032, 755. Anal. Calcd. for C23H31IO2: C, 59.23; H, 6.70. Found: C, 59.23; H, 6.72.

1. customAn oven-dried three-neck 500 mL round-bottom flask, which was equipped with a magnetic stir bar
2. customwas fitted with a reflux condenser
3. customThe flask was purged with argon
4. temperatureThe reaction mixture was heated
5. temperatureto reflux
6. temperatureat reflux for 1.5 h
7. customA separate oven-dried 2 L round bottom flask
8. customwhich was equipped with a magnetic stir bar
9. customfitted with a septum
10. customwas purged with argon
11. temperatureThe reaction mixture was cooled to −78° C.
12. stirringThe solution was stirred for 1 h
13. additionwas added via cannula over a 30 min period
14. stirringto stir at −78° C. for 1 h
15. temperatureThe reaction mixture was warmed to room temperature slowly where it
16. stirringwas stirred for an additional 12 h
17. temperatureThe mixture was then cooled to 0° C.
18. temperaturethe dark red solution was warmed to room temperature
19. stirringstirred for 1 h
20. customThe solvent was removed via a rotary evaporator
21. washwashed with a saturated solution of sodium sulfite
22. washwashed with brine
23. dry with materialThe organic layer was then dried over MgSO4
24. filtrationfiltered
25. customthe solvent was removed via rotary evaporator
26. customto give a yellow solid
27. customThe crude material was triturated with hexanes
28. filtrationfiltered

ORD-Eintrag

ord-6034289d25e54134844f571bd2540b85

Quelldatensatz

uspto-grants-2010_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07858784B2