Reaktion #49036

Reaktionsgleichung

(E)-3,4-Difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-[(3-methylcarbamoyl-propoxyimino)-methyl]-benzamide

(E)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-[(3-methylcarbamoyl-propoxyimino)-methyl]-benzamide

dichloroacetic acid

→

3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-(3-oxo-[1,2]oxazinan-2-ylmethyl)-benzamide

Ausbeute 91.0%

Lösungsmittel

methylene chloride

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeat room temperature
2. 2
   Sonstigedichloromethane was removed under reduced pressure with a rotary evaporator
3. 3
   workup.ADDITIONThe residue was diluted with 1,2-dichloroethane (240 ml)
4. 4
   workup.STIRRINGthe mixture was stirred at 60° C. for 8 hours
5. 5
   Filtrationfiltered
6. 6
   SonstigeThe residue obtained
7. 7
   Einengenby concentrating the filtrate
8. 8
   workup.ADDITIONwas diluted with ethyl acetate (800 ml)
9. 9
   Waschenwashed sequentially with water (400 ml), saturated aqueous sodium bicarbonate (400 ml), and saturated brine (400 ml)
10. 10
    TrocknenThe organic layer was dried over anhydrous sodium sulfate
11. 11
    Einengenconcentrated under reduced pressure
12. 12
    SonstigeThe residue was purified by silica gel column chromatography (CH2Cl2/MeOH (25:1))

Vorschrift

(E)-3,4-Difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-[(3-methylcarbamoyl-propoxyimino)-methyl]-benzamide (8.0 g, 13.5 mmol) obtained in Step C of Example 28 was suspended in methylene chloride (240 ml), and borane-pyridine complex (5.45 ml, 53.8 mmol) and dichloroacetic acid (6.65 ml, 80.8 mmol) were added thereto at room temperature. The reaction mixture was stirred at room temperature for 15 hours, and dichloromethane was removed under reduced pressure with a rotary evaporator. The residue was diluted with 1,2-dichloroethane (240 ml), and the mixture was stirred at 60° C. for 8 hours, and filtered. The residue obtained by concentrating the filtrate was diluted with ethyl acetate (800 ml), and washed sequentially with water (400 ml), saturated aqueous sodium bicarbonate (400 ml), and saturated brine (400 ml). The organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (CH2Cl2/MeOH (25:1)) to give 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-(3-oxo-[1,2]oxazinan-2-ylmethyl)-benzamide (Compound G-1, 6.93 g, 91% yield).

Quelle