反応 #5471

反応方程式

water

4-amino-5-chloro-2-hydroxybenzoic acid methyl ester

sodium hydride

allyl bromide

→

pale tan solid

収率 62.2%

4-Amino-5-chloro-2-(2-propenyloxy)benzoic acid

収率 62.2%

溶媒

dimethylformamide

反応条件

後処理

1. 1
   workup.STIRRINGThe mixture was stirred at 95°±5° C. for one hour
2. 2
   温度cooled to room temperature
3. 3
   その他The solid was removed by filtration
4. 4
   抽出the filtrate was extracted with ether (2×100 mL)
5. 5
   workup.ADDITIONtreated with potassium hydroxide (10 g)
6. 6
   温度refluxed for 45 minutes
7. 7
   その他The ethanol was removed in vacuo
8. 8
   抽出the aqueous solution was extracted with ether (50 mL) and petroleum ethers (30°-60°, 50 mL)
9. 9
   温度cooled (0° C.)
10. 10
    ろ過The suspension was filtered
11. 11
    その他dried
12. 12
    workup.DISSOLUTIONdissolved in methylene chloride (150 mL)
13. 13
    workup.ADDITIONcontaining a little methanol
14. 14
    乾燥dried (Na2SO4)
15. 15
    濃縮concentrated in vacuo
16. 16
    その他Trituration from cold ether/petroleum ethers (30°-60°) and recrystallization from ethyl acetate/hexane (2 crops)

実験手順

A suspension of 60% sodium hydride/oil dispersion (1.52 g, 38 mmol) in anhydrous dimethylformamide (50 mL) under nitrogen was treated in portions with 4-amino-5-chloro-2-hydroxybenzoic acid methyl ester (6.05 g, 30 mmol), stirred at room temperature for 30 minutes, and treated with allyl bromide (4.60 g, 38 mmol). The mixture was stirred at 95°±5° C. for one hour, cooled to room temperature, and added to water (250 mL). The solid was removed by filtration and saved, and the filtrate was extracted with ether (2×100 mL). The concentrated ethereal extracts were combined with the filtered solid, taken up in 20% aqueous ethanol (100 mL), treated with potassium hydroxide (10 g), and refluxed for 45 minutes. The ethanol was removed in vacuo and the aqueous solution was extracted with ether (50 mL) and petroleum ethers (30°-60°, 50 mL), cooled (0° C.), and acidified to pH 4 with concentrated hydrochloric acid (17 mL). The suspension was filtered and the solid was air dried, dissolved in methylene chloride (150 mL) containing a little methanol, dried (Na2SO4), and concentrated in vacuo. Trituration from cold ether/petroleum ethers (30°-60°) and recrystallization from ethyl acetate/hexane (2 crops) afforded 4.25 g (62.2%) of a pale tan solid; mp 136°-137° C.

出典