反应详情

温度

-3 °C

3-Hydroxymethyl-2-methyl phenol (113.9 g, 824.0 mmol) was dissolved in a mixture of acetonitrile (850 mL) and trifluoroacetic acid (750.0 mL, 9.735 mmol) in a 3-neck 5-L flask under nitrogen. The reaction mixture was cooled to −3° C. N-bromosuccinimide (141 g, 791 mmol) was added over 15 minutes, with the temperature during addition in the range of −35 to −33° C. The reaction mixture was allowed to stir for an additional 15 min during which time the temperature decreased to −40° C. The cooling bath was removed, and potassium carbonate (741.0 g, 5.358 mmol) diluted with water to a total of 1.0 L was added. Off-gassing was observed, and the temperature increased to 25° C. MTBE (1.5 L) was added, and the reaction mixture was transferred to a separatory funnel. The layers were separated. The aqueous layer was diluted with water (500 mL) and extracted with MTBE (1 L)+EtOAc (500 mL), and then MTBE (500 mL)+EtOAc (250 mL). The combined organic layers were washed with water (240 mL) and dried over sodium sulfate. The sodium sulfate was removed by filtration, washed with additional MTBE and concentrated under reduced pressure. MTBE (684 mL, 2 volumes) was added, and the suspension was heated to 40° C. to produce a homogeneous solution. The solution was allowed to cool to room temperature. Six volumes of heptane were added, and the suspension was stirred overnight. The suspension was filtered, and the crystals were washed with 4:1 heptane: MTBE (500 mL), followed by heptane (500 mL). The solid was dried under vacuum, providing 4-bromo-3-hydroxymethyl-2-methyl phenol. 1H NMR (400 MHz, DMSO-d6): δ 9.52 (s, 1H), 7.21 (d, J=8.6 Hz, 1H), 6.71 (d, J=8.6 Hz, 1H), 4.88 (t, J=5.1 Hz, 1H), 4.59 (d, J=5.1 Hz, 2H), 2.23 (s, 3H)

1. customdecreased to −40° C
2. customThe cooling bath was removed
3. additionwas added
4. temperaturethe temperature increased to 25° C
5. customthe reaction mixture was transferred to a separatory funnel
6. customThe layers were separated
7. additionThe aqueous layer was diluted with water (500 mL)
8. extractionextracted with MTBE (1 L)+EtOAc (500 mL)
9. washThe combined organic layers were washed with water (240 mL)
10. dry with materialdried over sodium sulfate
11. customThe sodium sulfate was removed by filtration
12. washwashed with additional MTBE
13. concentrationconcentrated under reduced pressure
14. additionMTBE (684 mL, 2 volumes) was added
15. temperaturethe suspension was heated to 40° C.
16. customto produce a homogeneous solution
17. temperatureto cool to room temperature
18. stirringthe suspension was stirred overnight
19. filtrationThe suspension was filtered
20. washthe crystals were washed with 4:1 heptane
21. customThe solid was dried under vacuum