Reaktion #1461804

Reaktionsgleichung

citric acid

thionyl chloride

1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one

4-(2-bromo-5-fluorophenyl)-2-hydroxy-4-methylvaleric acid-methyl ester

6-amino-4-methyl-2,3-benzoxazin-1-one

→

product

Ausbeute 80.6%

6-[4-(2-Bromo-5-fluorophenyl)-4-methyl-2-oxovaleroylamino]-4-methyl-2,3-benzoxazin-1-one

Ausbeute 80.6%

Lösungsmittel

dimethyl acetamide

dichloromethane

MTBE

MTBE

Reaktionsbedingungen

Aufarbeitung

1. 1
   Waschenwashed with a solution of 1.2 g of NaHCO3 and 4.0 g of Na2SO3 in 50 ml of water, saturated NaHCO3 and saturated NaCl
2. 2
   Trocknendried (Na2SO4)
3. 3
   Einengenconcentrated by evaporation in a vacuum
4. 4
   workup.ADDITIONmixed with 3.9 ml (3.9 mmol) of a 1 M sodium hydroxide solution
5. 5
   workup.WAITAfter 30 minutes
6. 6
   Einengenthe batch is concentrated in a vacuum
7. 7
   workup.ADDITIONdiluted with 20 ml of water
8. 8
   Waschenwashed with MTBE
9. 9
   Extraktionextracted with 100 ml of ethyl acetate and 100 ml of dichloromethane
10. 10
    TrocknenThe combined extracts are dried (NaSO4)
11. 11
    Einengenconcentrated by evaporation in a vacuum
12. 12
    workup.WAITAfter 20 minutes at −6° C.
13. 13
    WaschenThe organic phase is washed with saturated NaCl
14. 14
    Trocknendried (Na2SO4)
15. 15
    Einengenconcentrated by evaporation in a vacuum

Vorschrift

663 mg (1.56 mol) of 1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one (Dess-Martin-periodina cf. D. B. Dess, J. C. Martin, J. Am. Chem. Soc. 1991, 113, 7277) is added to a solution of 250 mg (0.78 mmol) of 4-(2-bromo-5-fluorophenyl)-2-hydroxy-4-methylvaleric acid-methyl ester in 10 ml of dichloromethane. After 1.5 hours at room temperature, the batch is diluted with 150 ml of MTBE, washed with a solution of 1.2 g of NaHCO3 and 4.0 g of Na2SO3 in 50 ml of water, saturated NaHCO3 and saturated NaCl, dried (Na2SO4) and concentrated by evaporation in a vacuum. The residue (250 mg) is taken up in 16 ml of THF-EtOH (1:1) and mixed with 3.9 ml (3.9 mmol) of a 1 M sodium hydroxide solution. After 30 minutes, the batch is concentrated in a vacuum, diluted with 20 ml of water and washed with MTBE. The aqueous phase is acidified with 10% sulfuric acid (pH 2) and extracted with 100 ml of ethyl acetate and 100 ml of dichloromethane. The combined extracts are dried (NaSO4) and concentrated by evaporation in a vacuum. 0.06 ml (0.92 mmol) of thionyl chloride is added in drops at −6° C. to the solution of the residue (230 mg) in 5 ml of dimethyl acetamide. After 20 minutes at −6° C., 201 mg (1.14 mmol) of 6-amino-4-methyl-2,3-benzoxazin-1-one is added to it. The batch is stirred for 15 hours at room temperature, acidified with 50 ml of 10% citric acid and shaken out with 150 ml of MTBE. The organic phase is washed with saturated NaCl, dried (Na2SO4) and concentrated by evaporation in a vacuum. Column chromatography on silica gel with hexane-ethyl acetate yields 290 mg of product.

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