Hydrochloric Acid → 1-[4-Fluoro-3-(tert-butoxycarbonylamino)phenyl]-2-(5-fluoro-2-methoxyphenyl)-2-methyl-1-propanone

HRID 578776

反応式

HRID 578776 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:12])[CH:9]([CH3:11])[CH3:10])=[CH:4][C:3]=1[NH:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15].Br[C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=1[O:29][CH3:30].F[B-](F)(F)F.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.CC(C)([O-])C.[Na+].Cl>O1CCCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:12])[C:9]([C:22]2[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=2[O:29][CH3:30])([CH3:10])[CH3:11])=[CH:4][C:3]=1[NH:13][C:14]([O:16][C:17]([CH3:18])([CH3:20])[CH3:19])=[O:15]

参加物

9

反応物 5

HCID 313Hydrochloric AcidHCID 1362922-Bromo-4-fluoroanisoleHCID 23676156Sodium t-butoxideHCID 44558591Tri-t-butylphosphine fluoroborateHCID 580223281-[4-Fluoro-3-(tert-butoxycarbonylamino)phenyl]-2-methyl-1-propanone

生成物 1

HCID 689917521-[4-Fluoro-3-(tert-butoxycarbonylamino)phenyl]-2-(5-fluoro-2-methoxyphenyl)-2-methyl-1-propanone

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
70 °C

実験手順

A mixture of 1-[4-fluoro-3-(tert-butoxycarbonyl -amino)phenyl]-2-methyl-1-propanone (0.11 g), 2-bromo-4-fluoroanisole (0.057 mL), palladium(II) acetate (4.5 mg), tri(tert-butyl)phosphine tetrafluoroborate (5.8 mg) and sodium tert-butoxide (96 mg) in tetrahydrofuran (1 mL) was stirred at 70° C. under an argon atmosphere for 3 days. To the reaction mixture was added water, and the mixture was stirred for 10 minutes. The mixture was poured into 1 mol/L hydrochloric acid, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine successively, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=10/1) to give 1-[4-fluoro-3-(tert-butoxycarbonylamino)phenyl]-2-(5-fluoro -2-methoxyphenyl)-2-methyl-1-propanone (45 mg). This material was dissolved in hydrochloric acid (4 mol/L ethyl acetate solution, 3 mL), and the mixture was stirred at room temperature overnight. The reaction mixture was poured into a saturated aqueous sodium hydrogen carbonate solution, and the resulting mixture was extracted with ethyl acetate. The extract was washed with brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on aminopropylated silica gel (eluent: n-hexane/ethyl acetate=4/1 -3/1) to give the title compound (25 mg).

後処理

  1. stirringthe mixture was stirred for 10 minutes
  2. extractionthe resulting mixture was extracted with ethyl acetate
  3. washThe extract was washed with water and brine successively
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was removed under reduced pressure
  6. customthe residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=10/1)

出典と根拠

ORDレコード
ord-8b57d600bee741c4b3bb50dc1965b622
出典データセット
uspto-grants-2015_05
特許番号
US09040693B2

関連ノート

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