反応 #2186183

反応方程式

sodium nitrite

triisopropyl borate

hydrogen peroxide

compound ( C2 )

1-bromo-3-chloro-4-ethoxy-2-fluorobenzene

sec-BuLi

→

3-chloro-4-ethoxy-2-fluorophenol

収率 70.1%

溶媒

ethyl acetate

THF

acetic acid

THF

反応条件

後処理

1. 1
   workup.ADDITIONthe dropwise addition
2. 2
   workup.DISSOLUTIONdissolved
3. 3
   workup.ADDITIONtherein was added dropwise to the resulting solution in a temperature range of −70 to −75° C.
4. 4
   workup.ADDITIONthe dropwise addition
5. 5
   workup.STIRRINGthe mixture was stirred for 1 hour in that temperature range
6. 6
   workup.STIRRINGby stirring over night
7. 7
   workup.STIRRINGby stirring for 30 minutes
8. 8
   その他slowly at room temperature
9. 9
   workup.ADDITIONthe dropwise addition
10. 10
    workup.STIRRINGthe mixture was stirred for 4.5 hours at room temperature
11. 11
    workup.ADDITIONby mixing
12. 12
    workup.WAITthe mixture was left at rest
13. 13
    その他to separate into an organic layer
14. 14
    抽出by extracting to the organic layer
15. 15
    洗浄The resulting organic layer was washed sequentially with water
16. 16
    乾燥a saturated sodium chloride aqueous solution, dried over anhydrous magnesium sulfate
17. 17
    濃縮concentrated under reduced pressure
18. 18
    その他to obtain a residue
19. 19
    その他30.97 g of the residue was purified by a preparative column chromatography

実験手順

30.02 g of the compound (C2) was dissolved in 300 mL of THF. sec-BuLi (1.01 M solution, 124 mL) was added dropwise to the resulting solution in a temperature range of −70 to −75° C., and after completing the dropwise addition, the mixture was stirred for 1 hour in that temperature range. 40 mL of a THF solution having 18.71 g triisopropyl borate dissolved therein was added dropwise to the resulting solution in a temperature range of −70 to −75° C., and after completing the dropwise addition, the mixture was stirred for 1 hour in that temperature range. Thereafter, the temperature of the solution was gradually increased to room temperature, followed by stirring over night. After adding 11.92 g of acetic acid to the reaction mixture, followed by stirring for 30 minutes, 29.95 g of hydrogen peroxide was added dropwise thereto slowly at room temperature, and after completing the dropwise addition, the mixture was stirred for 4.5 hours at room temperature. A sodium nitrite aqueous solution and ethyl acetate were added to the reaction mixture, followed by mixing, and the mixture was left at rest to separate into an organic layer and an aqueous layer, followed by extracting to the organic layer. The resulting organic layer was washed sequentially with water and a saturated sodium chloride aqueous solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a residue. The residue was a yellowish solid. 30.97 g of the residue was purified by a preparative column chromatography using a mixed solvent of heptane and ethyl acetate (heptane/ethyl acetate=5/1 by volume) as a developing solvent and silica gel as a mediator to obtain 13.29 g of 3-chloro-4-ethoxy-2-fluorophenol (b64). The resulting compound (b64) was a yellowish solid.

出典