Reaction #5471

Reaction equation

water

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

sodium hydride

allyl bromide

→

pale tan solid

Yield 62.2%

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

Yield 62.2%

Solvents

dimethylformamide

Conditions

Workup

1. 1
   workup.STIRRINGThe mixture was stirred at 95°±5° C. for one hour
2. 2
   Temperaturecooled to room temperature
3. 3
   OtherThe solid was removed by filtration
4. 4
   Extractionthe filtrate was extracted with ether (2×100 mL)
5. 5
   workup.ADDITIONtreated with potassium hydroxide (10 g)
6. 6
   Temperaturerefluxed for 45 minutes
7. 7
   OtherThe ethanol was removed in vacuo
8. 8
   Extractionthe aqueous solution was extracted with ether (50 mL) and petroleum ethers (30°-60°, 50 mL)
9. 9
   Temperaturecooled (0° C.)
10. 10
    FiltrationThe suspension was filtered
11. 11
    Otherdried
12. 12
    workup.DISSOLUTIONdissolved in methylene chloride (150 mL)
13. 13
    workup.ADDITIONcontaining a little methanol
14. 14
    Dryingdried (Na2SO4)
15. 15
    Concentrationconcentrated in vacuo
16. 16
    OtherTrituration from cold ether/petroleum ethers (30°-60°) and recrystallization from ethyl acetate/hexane (2 crops)

Procedure

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.

Source