Réaction #2545

Équation de réaction

N-Bromosuccinimide

calcium carbonate

sodium borohydride

ammonium chloride

m-toluyl chloride

o-anisidine

sodium hydroxide

→

title compound

Rendement 66.1%

3-Hydroxymethyl-N-(2-methoxyphenyl)benzamide

Rendement 66.1%

Solvants

dioxane water

acetone

methanol

carbon tetrachloride

THF

Conditions de réaction

Traitement

1. 1
   Températureheated
2. 2
   Températureunder reflux for 4 hours
3. 3
   ConcentrationAfter concentrating the reaction solution to 1/3 volume, insoluble materials
4. 4
   Autrewere removed by filtration
5. 5
   TempératureTo the resulting filtrate cooled in an ice bath
6. 6
   AutreThe resulting reaction mixture
7. 7
   Extractionextracted with methylene chloride
8. 8
   Lavagewashed with 10% citric acid aqueous solution, water and saturated brine in that order
9. 9
   SéchageAfter drying on anhydrous magnesium sulfate
10. 10
    Autreremoving the solvent
11. 11
    Autreby evaporation
12. 12
    Autreto obtain creamy-colored powder
13. 13
    workup.ADDITIONTo this were added
14. 14
    Températureof heating
15. 15
    Températureunder reflux
16. 16
    Filtrationfiltering off the formed insoluble materials
17. 17
    Autrethe organic solvent was removed by evaporation
18. 18
    ExtractionThe resulting residue was extracted with ethyl acetate
19. 19
    Lavagethe organic layer was washed with saturated brine
20. 20
    Séchagedried on anhydrous magnesium sulfate
21. 21
    Autrefollowed by the removal of the solvent by evaporation
22. 22
    Autreto obtain an orange oily material
23. 23
    workup.STIRRINGAfter 1 hour of stirring at the same temperature
24. 24
    Températurewarmed to room temperature
25. 25
    AutreAfter removing methanol
26. 26
    Autreby evaporation, ethyl acetate extraction
27. 27
    Lavagethe resulting organic layer was washed with saturated brine
28. 28
    Séchagedried on anhydrous magnesium sulfate
29. 29
    Autresubjected to evaporation
30. 30
    Autreto remove the solvent
31. 31
    Lavagethe resulting colorless solid material was washed with an ether-hexane (2:1) mixture solution

Mode opératoire

N-Bromosuccinimide (1.29 g, 7.2 mmol) and AIBN (50 mg, 0.30 mmol) were suspended in carbon tetrachloride (80 ml), mixed with m-toluyl chloride (0.8 ml, 6.0 mmol) and then heated under reflux for 4 hours while exposing to light. After concentrating the reaction solution to 1/3 volume, insoluble materials were removed by filtration. To the resulting filtrate cooled in an ice bath were added dropwise o-anisidine (0.69 ml, 6 mmol) and 20% sodium hydroxide aqueous solution (5 ml) in that order. The resulting reaction mixture was stirred for 20 minutes at room temperature, extracted with methylene chloride and then washed with 10% citric acid aqueous solution, water and saturated brine in that order. After drying on anhydrous magnesium sulfate and removing the solvent by evaporation, the resulting light beige solid material was subjected to silica gel column chromatography (ether:hexane=1:1) to obtain creamy-colored powder. To this were added precipitated calcium carbonate (2.34 g, 23.4 mmol) and a dioxane-water (1:1) mixture solution (20 ml), followed by 6 hours of heating under reflux. After adding THF (50 ml) and filtering off the formed insoluble materials, the organic solvent was removed by evaporation. The resulting residue was extracted with ethyl acetate, and the organic layer was washed with saturated brine and dried on anhydrous magnesium sulfate, followed by the removal of the solvent by evaporation to obtain an orange oily material. This was dissolved in methanol (15 ml), and sodium borohydride (90 mg, 2.34 mmol) was added to the solution in one portion at -15° C. After 1 hour of stirring at the same temperature, the reaction mixture was mixed with acetone (1 ml), warmed to room temperature and then mixed with saturated ammonium chloride aqueous solution (10 ml). After removing methanol by evaporation, ethyl acetate extraction was carried out, and the resulting organic layer was washed with saturated brine, dried on anhydrous magnesium sulfate and then subjected to evaporation to remove the solvent. The thus obtained residue was subjected to silica gel column chromatography (ether:hexane=3:1), and the resulting colorless solid material was washed with an ether-hexane (2:1) mixture solution to obtain 1.02 g (66.1%) of the title compound in the form of colorless powder.

Source