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

HRID 2038600ノート

反応式

HRID 2038600 の反応式
[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]

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

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.

後処理

  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))

出典と根拠

ORDレコード
ord-340d6b17e61540ed8c71642183724068
出典データセット
uspto-grants-2013_11
特許番号
US08575391B2

反応ノート

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