Reaktion #1050558

Reaktionsgleichung

Magnesium

N-methoxy-N-methyl-4-amino-5-chloro-2-methoxybenzamide

chlorotrimethylsilane

magnesium

1-bromo-2-chlorobutane

1-bromo-4-chlorobutane

→

1-(4-amino-5-chloro-2-methoxyphenyl)-5-chloropentan-1-one

Ausbeute 81.1%

Lösungsmittel

ethyl acetate

THF

THF

hydrochloric acid

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeremained below 25° C
2. 2
   Temperaturto warm to between -12 and 30° C.
3. 3
   workup.ADDITIONwas added over approximately 20 minutes
4. 4
   TemperaturThe mixture was heated to 32° C.
5. 5
   SonstigeThe organic layer was separated
6. 6
   Waschenwashed sequentially with 2 L of water and 2 L of 1:1 water/saturated sodium chloride solution and saturated sodium chloride solution
7. 7
   Extraktionextracted with ethyl acetate
8. 8
   Trocknendried over sodium sulfate
9. 9
   Filtrationfiltered
10. 10
    Einengenconcentrated
11. 11
    workup.WAITto stand at room temperature for approximately 12 hours
12. 12
    Sonstigegiving a precipitate
13. 13
    SonstigeThe precipitate was isolated by filtration
14. 14
    Waschenwashed with hexane
15. 15
    SonstigeDrying in a vacuum oven at between 50 and 55° C. under a nitrogen gas

Vorschrift

Magnesium (236 g, 9.71 mol) was suspended in 3.5 L of THF under nitrogen and 1-bromo-4-chlorobutane (1.11 L, 8.68M, 9.63 mol) was added at a rate such that the temperature of the mixture remained below 25° C. A solution of N-methoxy-N-methyl-4-amino-5-chloro-2-methoxybenzamide (400 g, 1.64 mol), prepared as in Example 2, under nitrogen in 4 L of THF was cooled to -20° C. and 410 mL of chlorotrimethylsilane was added. The mixture was allowed to warm to between -12 and 30° C. and then 2.5 L of the solution containing the magnesium and 1-bromo-2-chlorobutane was added over approximately 20 minutes. The mixture was cooled to 50° C. and then diluted with 420 mL of concentrated hydrochloric acid in 5 L of water. The mixture was heated to 32° C., stirred for 15 minutes and then diluted with approximately 2 L of ethyl acetate. The organic layer was separated and washed sequentially with 2 L of water and 2 L of 1:1 water/saturated sodium chloride solution and saturated sodium chloride solution. All aqueous layers were combined and extracted with ethyl acetate. All organic layers were combined, dried over sodium sulfate, filtered and concentrated. The residue was combined with hot hexane and allowed to stand at room temperature for approximately 12 hours giving a precipitate. The precipitate was isolated by filtration and washed with hexane. Drying in a vacuum oven at between 50 and 55° C. under a nitrogen gas bleed gave 1-(4-amino-5-chloro-2-methoxyphenyl)-5-chloropentan-1-one (365 g, 1.33 mol).

Quelle