Dichloroacetic Acid → 3,4-Difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-(3-oxo-isoxazolidin-2-ylmethyl)-benzamide

HRID 20759

반응식

HRID 20759 반응식
[F:1][C:2]1[C:3]([NH:25][C:26]2[CH:31]=[CH:30][C:29]([I:32])=[CH:28][C:27]=2[F:33])=[C:4]([CH:12]=[C:13](/[CH:16]=[N:17]/[O:18][CH2:19][CH2:20][C:21](=[O:24])NC)[C:14]=1[F:15])[C:5]([NH:7][O:8][CH2:9][CH2:10][OH:11])=[O:6].ClC(Cl)C(O)=O>ClCCl>[F:1][C:2]1[C:3]([NH:25][C:26]2[CH:31]=[CH:30][C:29]([I:32])=[CH:28][C:27]=2[F:33])=[C:4]([CH:12]=[C:13]([CH2:16][N:17]2[C:21](=[O:24])[CH2:20][CH2:19][O:18]2)[C:14]=1[F:15])[C:5]([NH:7][O:8][CH2:9][CH2:10][OH:11])=[O:6]

참가 물질

4

반응물 2

HCID 6597Dichloroacetic AcidHCID 113652433,4-difluoro-2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-5-[(E)-[3-(methylamino)-3-oxopropoxy]iminomethyl]benzamide

생성물 1

HCID 116281803,4-Difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-(3-oxo-isoxazolidin-2-ylmethyl)-benzamide수율 96.7%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To (E)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-[(2-methylcarbamoyl-ethoxyimino)-methyl]-benzamide (9.60 g, 15.54 mmol) were added sequentially dichloromethane (300 ml) and borane-pyridine complex (11.70 ml, 115.80 mmol) to give a suspension. This mixture was stirred at room temperature, and dichloroacetic acid (9.51 ml, 115.80 mmol) was added dropwise thereto over 10 minutes. After the mixture was stirred at room temperature for 13 hours, dichloromethane was removed under reduced pressure with a rotary evaporator, and the resultant residue was diluted with 1,2-dichloroethane (300 ml). This mixture was stirred at 60° C. for 6 hours, diluted with ethyl acetate, and washed sequentially with 0.1 M aqueous hydrochloric acid, saturated aqueous sodium bicarbonate, and saturated aqueous sodium chloride. The organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give the title compound (8.28 g, 90% yield).

후처리

  1. customto give a suspension
  2. stirringAfter the mixture was stirred at room temperature for 13 hours
  3. customdichloromethane was removed under reduced pressure with a rotary evaporator
  4. additionthe resultant residue was diluted with 1,2-dichloroethane (300 ml)
  5. stirringThis mixture was stirred at 60° C. for 6 hours
  6. additiondiluted with ethyl acetate
  7. washwashed sequentially with 0.1 M aqueous hydrochloric acid, saturated aqueous sodium bicarbonate, and saturated aqueous sodium chloride
  8. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by silica gel column chromatography

출처 및 근거

ORD 기록
ord-42fea69114ec426eaf64cb41d23a22e9
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07745663B2

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