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

HRID 2038635

반응식

HRID 2038635 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-691075d35f7c489c9a6443b7b4774b8a
출처 데이터셋
uspto-grants-2013_11
특허 번호
US08575391B2

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