反応 #1833226

反応方程式

diisopropylamine

n-BuLi

NaH

Methyl iodide

trimethylborate

peracetic acid

5-bromo-2,2-difluorobenzo[d][1,3]dioxole

NaH

HCl

NaHSO3

→

LDA

title compound

収率 31.2%

5-Bromo-2,2-difluoro-4-methoxybenzo[d][1,3]dioxole

収率 31.2%

溶媒

tetrahydrofuran

water

NaCl

反応条件

後処理

1. 1
   温度to warm to ambient overnight
2. 2
   温度The mixture was cooled to −30 to −40° C.
3. 3
   workup.STIRRINGThe mixture was stirred for 30 min at −30° C.
4. 4
   温度warmed to 5-10° C.
5. 5
   workup.STIRRINGstirred for 20 min
6. 6
   抽出The mixture was extracted ethyl acetate (2×100 mL)
7. 7
   洗浄the combined extracts were washed with saturated NaCl (50 mL)
8. 8
   乾燥dried (Na2SO4) and rotary evaporated
9. 9
   workup.DISSOLUTIONThe crude phenol was dissolved in dry DMSO (50 mL)
10. 10
    workup.STIRRINGstirred for 30 min
11. 11
    その他to produce a clear solution
12. 12
    workup.STIRRINGthe mixture was stirred for 20 h at 20° C
13. 13
    workup.STIRRINGstirring
14. 14
    workup.WAITwas continued for 1 h
15. 15
    抽出extracted diethyl ether (2×75 mL)
16. 16
    洗浄The combined extracts were washed with water (2×20 mL), with saturated NaCl (20 mL)
17. 17
    乾燥dried (Na2SO4)
18. 18
    その他evaporated
19. 19
    その他The crude material was purified by chromatography on silica with a 0-20% ethyl acetate-hexane gradient

実験手順

A solution of LDA was prepared from diisopropylamine (4.2 g, 41 mmol) and n-BuLi (2.5 M; 15.4 mL, 38 mmol) in dry tetrahydrofuran (100 mL). The solution was cooled to −70° C. and treated in portions with 5-bromo-2,2-difluorobenzo[d][1,3]dioxole (7.0 g, 30 mmol). After 2 h at −70° C., trimethylborate (4.3 g, 41 mmol) was added in portions, stirred at −70° C. for 1.5 h and then allowed to warm to ambient overnight. The mixture was cooled to −30 to −40° C. and treated carefully with 28% peracetic acid. The mixture was stirred for 30 min at −30° C., warmed to 5-10° C., treated with 10% NaHSO3 (100 mL) solution and stirred for 20 min. The mixture was acidified by addition of 6 M HCl and diluted with saturated NaCl solution (75 mL). The mixture was extracted ethyl acetate (2×100 mL) and the combined extracts were washed with saturated NaCl (50 mL), dried (Na2SO4) and rotary evaporated. The crude phenol was dissolved in dry DMSO (50 mL), treated with 95% NaH (750 mg, 30 mmol) and stirred for 30 min to produce a clear solution. Methyl iodide (5.0 g, 35 mmol) was added in portions, and the mixture was stirred for 20 h at 20° C. An additional 200 mg NaH were added and stirring was continued for 1 h more. The mixture was poured into water (100 mL) and extracted diethyl ether (2×75 mL). The combined extracts were washed with water (2×20 mL), with saturated NaCl (20 mL), dried (Na2SO4) and evaporated. The crude material was purified by chromatography on silica with a 0-20% ethyl acetate-hexane gradient to afford the title compound as a clear liquid (2.5 g, 31%): 1H NMR (400 MHz, CDCl3) δ 7.25 (d, J=8.5 Hz, 1H), 6.63 (d, J=8.5 Hz, 1H), 4.13 (s, 3H); 19F NMR (376 MHz, CDCl3) δ −49.66; EIMS m/z 266.

出典