Reacción #5472

Ecuación de reacción

sodium hydride oil dispersion

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

(2-chloroethyl)methyl sulfide

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product

Rendimiento 57.0%

4-Amino-5-chloro-2-[2-(methylthio)ethoxy]benzoic acid

Rendimiento 57.0%

Disolventes

dimethylformamide

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaA cooled
2. 2
   Temperaturaheated to 100° C. for 18 hours
3. 3
   TemperaturaThe solution is cooled
4. 4
   Concentraciónconcentrated in vacuo
5. 5
   workup.ADDITIONadded to water (25 mL)
6. 6
   ExtracciónThe aqueous solution is extracted with ether
7. 7
   Secadothe extract is dried (MgSO4)
8. 8
   Concentraciónconcentrated in vacuo
9. 9
   workup.ADDITIONtreated with potassium hydroxide (5.0 g)
10. 10
    Temperaturarefluxed for one hour
11. 11
    ConcentraciónThe mixture is concentrated
12. 12
    workup.ADDITIONdiluted with water to 75 mL total volume
13. 13
    Extracciónextracted with ether
14. 14
    FiltraciónThe precipitate is filtered
15. 15
    Lavadowashed with water, air
16. 16
    Otrodried
17. 17
    Otrorecrystallized from ethyl acetate

Procedimiento

A cooled (5° C.) suspension of 60% sodium hydride oil dispersion (0.52 g, 13 mmoles) in anhydrous dimethylformamide (15 mL) under nitrogen was treated in portions with 4-amino-5-chloro-2-hydroxybenzoic acid (0.94 g, 5 mmoles), stirred for 15 minutes at 25° C., treated with (2-chloroethyl)methyl sulfide (1.66 g, 15 mmoles), and heated to 100° C. for 18 hours. The solution is cooled, concentrated in vacuo, and added to water (25 mL). The aqueous solution is extracted with ether, and the extract is dried (MgSO4), concentrated in vacuo, taken up in 50% aqueous ethanol (50 mL), treated with potassium hydroxide (5.0 g), and refluxed for one hour. The mixture is concentrated, diluted with water to 75 mL total volume, extracted with ether, and acidified to pH 3 with concentrated HCl. The precipitate is filtered, washed with water, air dried, and recrystallized from ethyl acetate to afford 0.74 g (57%) of product as fine voluminous white needles, mp 137.5°-139.5° C.

Fuente