反应详情

To a solution of 2-bromo-1,4-bis(methyloxy)benzene (2.0 g, 9.21 mmol) and benzoyl chloride (1.229 mL, 10.596 mmol, 1.15 eq) in DCM (9.5 mL, C=1.0M) at 0° C. was added triflic acid (0.815 mL, 9.21 mmol) over 5 min. The reaction mixture was allowed to warm to ambient temperature (40 min) and then slowly heated to gentle reflux (oil bath at 42° C.) and stirred for 48 h. The reaction mixture was cooled to r.t., and MeOH (0.3 mL) was added and stirring was continued for 30 min. The reaction mixture was poured into 80 mL of ice cooled water. The aqueous layer was neutralized with a 1 M NaOH solution. The layers were separated. The aqueous layer was extracted twice with DCM (2×20 mL). The combined organic phase was washed twice with a 1/1 water/brine mixture (2×30 mL), dried over MgSO4, filtered and concentrated in vacuo to a brown-orange oil. Then, MTBE (7 mL) was added and the mixture was stirred into an ultra-sound bath. The resulting solid was filtered, rinsed with 1:1 MTBE/hexanes mixture and air dried to afford [4-bromo-2,5-bis(methyloxy)phenyl](phenyl)methanone in 76% yield (2.258 g) as a white solid. 1H NMR (300 MHz, DMSO) δ 7.72 (d, J=8.5 Hz, 1H), 7.65 (t, J=7.4 Hz, 1H), 7.51 (t, J=7.6 Hz, 1H), 7.45 (s, 1H), 7.10 (s, 1H), 3.81 (s, 2H), 3.63 (s, 2H), 13C NMR (75 MHz, DMSO) δ 194.5 (C═O), 150.7 (C), 149.7 (C), 136.7 (C), 133.5 (CH), 129.3 (2CH), 128.6 (2CH), 128.2 (C), 117.3 (CH), 113.3 (C), 112.5 (CH), 56.7 (OCH3), 56.5 (OCH3); MS (ESI) m/z: 321.1, 323.0 [M+H, 79Br, 81Br]+; 243.1, 245.0 [M-Ph, 79Br, 81Br]+.

1. temperatureslowly heated
2. temperatureto gentle reflux (oil bath at 42° C.)
3. temperatureThe reaction mixture was cooled to r.t.
4. stirringstirring
5. waitwas continued for 30 min
6. customThe layers were separated
7. extractionThe aqueous layer was extracted twice with DCM (2×20 mL)
8. washThe combined organic phase was washed twice with a 1/1 water/brine mixture (2×30 mL)
9. dry with materialdried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated in vacuo to a brown-orange oil
12. additionThen, MTBE (7 mL) was added
13. stirringthe mixture was stirred into an ultra-sound bath
14. filtrationThe resulting solid was filtered
15. washrinsed with 1:1 MTBE/hexanes mixture and air
16. customdried