반응 #49005

반응 방정식

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

dichloroacetic acid

→

3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-[(2-methylsulfanyl-ethoxyamino)-methyl]-benzamide

수율 104.6%

용매

methylene chloride

반응 조건

후처리

1. 1
   온도with cooling the reaction vessel in an ice-bath under a nitrogen atmosphere
2. 2
   기타The ice-bath was removed
3. 3
   기타After completion of the reaction
4. 4
   추출the reaction mixture was extracted with ethyl acetate
5. 5
   세척the organic layer was washed sequentially with water and saturated brine
6. 6
   건조dried over anhydrous Na2SO4
7. 7
   농축concentrated under reduced pressure
8. 8
   기타The resultant yellow residue was purified by silica gel column chromatography (Mega Bond Elut, Varian, 5% methanol/methylene chloride as an eluent)
9. 9
   농축The resultant fraction was concentrated under reduced pressure
10. 10
    기타the oily residue was triturated with 5% ethyl acetate/hexane

실험 절차

Namely, (E)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-[(2-methylsulfanyl-ethyoxyimino)-methyl]-benzamide (104.8 mg, 0.184 mmol) was dissolved in methylene chloride (anhydrous, 10 mL). Borane-pyridine complex (140 μL, 1.38 mmol) and then dichloroacetic acid (115 μL, 1.38 mmol) were added thereto with cooling the reaction vessel in an ice-bath under a nitrogen atmosphere. The ice-bath was removed, and the mixture was stirred at room temperature for 17 hours. After completion of the reaction, the reaction mixture was extracted with ethyl acetate, and the organic layer was washed sequentially with water and saturated brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The resultant yellow residue was purified by silica gel column chromatography (Mega Bond Elut, Varian, 5% methanol/methylene chloride as an eluent). The resultant fraction was concentrated under reduced pressure and the oily residue was triturated with 5% ethyl acetate/hexane to give 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-[(2-methylsulfanyl-ethoxyamino)-methyl]-benzamide (110 mg) as a white solid.

출처