反应详情

Bromine (3.7 mL, 11.6 g, 72.5 mmol, 1 equiv) was added via syringe to a solution of 2,4-di-t-butyl-phenol (15 g, 72.8 mmol, 1 equiv) in CH2Cl2 (200 ml). The brown color of Br2 disappeared upon addition. GC-MS analysis after 5 min shows only the presence of the desired brominated product (M+=286). The organic mixture was washed with water, then dried over MgSO4, and filtered. Upon removal of volatile material by rotary evaporation, a golden oil was obtained which solidified after placing under high vacuum (<1 mTorr). This material (4,6-di-t-butyl-2-bromophenol) was dissolved in dry THF (200 mL), under argon, and was deprotonated with NaH (1.92 g, 80 mmol, 1.1 equiv). After the addition of NaH the reaction mixture was stirred for 1 h at room temperature then MOMCl (6.1 mL, 6.5 g, 80.3 mmol, 1.1 equiv) was added via syringe. The reaction mixture was stirred at room temperature for 9 h. Water was added and the mixture was concentrated under vacuum to remove the THF. The desired product was extracted with CH2Cl2 (three times). The combined organic fractions were dried over MgSO4, filtered, and concentrated to ˜50 mL. CaH2 was added and stirred at room temperature for 6 h then at 100° C., under vacuum, for 1 h. The reaction vessel was sealed with a needle valve and brought inside an inert atmosphere glove box. The mixture was filtered through a pad of activated alumina with the aid of some Et2O. Volatiles were removed under vacuum to give 23.5 g (98% yield over two steps) of desired product 1-methoxymethylether-2,4-di-t-butyl-6-bromobenzene, as a golden oil. 1H NMR (300 MHz, CDCl3) δ: 1.30 (s, 9H, C(CH3)3), 1.44 (s, 9H, C(CH3)3), 3.70 (s, 3H, OCH3), 5.23 (s, 2H, OCH2O), 7.32 (d, 2H, aryl-H, 4J=2.4 Hz), 7.41 (d, 2H, aryl-H, 4J=2.4 Hz). 13C NMR (75 MHz, CDCl3) δ: 31.0 (C(CH3)3), 31.5 (C(CH3)3), 34.8 (C(CH3)3), 36.1 (C(CH3)3), 57.9 (OCH3), 99.5 (OCH2O), 117.7, 124.1, 128.9, 144.6, 147.8, 150.7 (aryl). GC-MS: M+=328.

1. washThe organic mixture was washed with water
2. dry with materialdried over MgSO4
3. filtrationfiltered
4. customUpon removal of volatile material
5. customby rotary evaporation
6. customa golden oil was obtained which
7. stirringThe reaction mixture was stirred at room temperature for 9 h
8. concentrationthe mixture was concentrated under vacuum
9. customto remove the THF
10. extractionThe desired product was extracted with CH2Cl2 (three times)
11. dry with materialThe combined organic fractions were dried over MgSO4
12. filtrationfiltered
13. concentrationconcentrated to ˜50 mL
14. additionCaH2 was added
15. stirringstirred at room temperature for 6 h
16. waitat 100° C., under vacuum, for 1 h
17. customThe reaction vessel was sealed with a needle valve
18. custombrought inside an inert atmosphere glove box
19. filtrationThe mixture was filtered through a pad of activated alumina with the aid of some Et2O
20. customVolatiles were removed under vacuum