تفاعل #49036

معادلة التفاعل

(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

المردود 91.0%

المذيبات

methylene chloride

ظروف التفاعل

المعالجة

1. 1
   أخرىat room temperature
2. 2
   أخرىdichloromethane 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
   ترشيحfiltered
6. 6
   أخرىThe residue obtained
7. 7
   تركيزby concentrating the filtrate
8. 8
   workup.ADDITIONwas diluted with ethyl acetate (800 ml)
9. 9
   غسيلwashed sequentially with water (400 ml), saturated aqueous sodium bicarbonate (400 ml), and saturated brine (400 ml)
10. 10
    تجفيفThe organic layer was dried over anhydrous sodium sulfate
11. 11
    تركيزconcentrated under reduced pressure
12. 12
    أخرىThe residue was purified by silica gel column chromatography (CH2Cl2/MeOH (25:1))

الإجراء التجريبي

(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).

المصدر