Trifluoroacetic acid → 3,4-Difluoro-2-[(2-Fluoro-4-Iodophenyl)amino]-N-(2-Hydroxyethoxy)-5-[(2-Hydroxyethoxy)methyl]benzamide

HRID 20724노트

반응식

HRID 20724 반응식
[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[C:7]([F:29])=[C:8]([F:28])[C:9]([NH:19][C:20]2[CH:25]=[CH:24][C:23]([I:26])=[CH:22][C:21]=2[F:27])=[C:10]([CH:18]=1)[C:11]([NH:13][O:14][CH2:15][CH2:16][OH:17])=[O:12].[BH4-].[Na+].FC(F)(F)C(O)=O.C(=O)(O)[O-].[Na+]>C1COCC1>[F:28][C:8]1[C:9]([NH:19][C:20]2[CH:25]=[CH:24][C:23]([I:26])=[CH:22][C:21]=2[F:27])=[C:10]([CH:18]=[C:6]([CH2:2][O:1][CH2:5][CH2:4][OH:3])[C:7]=1[F:29])[C:11]([NH:13][O:14][CH2:15][CH2:16][OH:17])=[O:12]

참가 물질

6

반응물 4

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 593480285-[1,3]dioxolan-2-yl-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-benzamide

생성물 1

HCID 115337913,4-Difluoro-2-[(2-Fluoro-4-Iodophenyl)amino]-N-(2-Hydroxyethoxy)-5-[(2-Hydroxyethoxy)methyl]benzamide수율 80%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of 5-[1,3]dioxolan-2-yl-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-benzamide (21.69 g) obtained in Step G in anhydrous THF (100 ml) were added sodium borohydride (4.21 g, 111.4 mmol) and trifluoroacetic acid (5.08 ml, 66.8 mmol) with ice-cooling, and the mixture was stirred at room temperature overnight. The reaction mixture was poured into saturated aqueous sodium bicarbonate, and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (SiO2 600 g, 100% AcOEt to AcOEt/MeOH (50:1 to 20:1)) to give 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-(2-hydroxy-ethoxymethyl)-benzamide (13.9 g, 80%) as a white powder.

후처리

  1. temperaturecooling
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with saturated aqueous sodium bicarbonate and saturated brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (SiO2 600 g, 100% AcOEt to AcOEt/MeOH (50:1 to 20:1))

출처 및 근거

ORD 기록
ord-8c1f75a1519a4c70ab298985d235dc5d
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07745663B2

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