Boron tribromide → 4-(3-Chloro-4-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)hexanal

HRID 1362541ノート

反応式

HRID 1362541 の反応式
[Cl:1][C:2]1[C:3]([O:32][CH3:33])=[C:4]([C@H:9]([CH2:30][CH3:31])[CH2:10][C@:11]([OH:29])([C:25]([F:28])([F:27])[F:26])C=NC2C=CC=C3C=2C=CC(=O)N3)[CH:5]=[CH:6][C:7]=1[F:8].B(Br)(Br)Br.[C:38]([O-])(O)=[O:39].[Na+]>C(Cl)Cl>[Cl:1][C:2]1[C:3]([O:32][CH3:33])=[C:4]([CH:9]([CH2:30][CH3:31])[CH2:10][C:11]([OH:29])([C:25]([F:27])([F:26])[F:28])[CH:38]=[O:39])[CH:5]=[CH:6][C:7]=1[F:8]

参加物

5

反応物 3

HCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 669693885-{[(2R,4R)-4-(3-chloro-4-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)hexylidene]amino}quinolin-2(1H)-one

生成物 1

HCID 866153364-(3-Chloro-4-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)hexanal

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

反応条件

温度
-30 °C

実験手順

and 2.3 g of (2R,4R/S)-4-(,4-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)hexanal 300 mg (0.88 mmol) of (2R,4R)-4-(3-chloro-4-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)hexanal and 140 mg (0.88 mmol) of 5-aminoquinolin-2(1H)-one are dissolved in 19 ml of toluene and the solution is admixed with 0.55 ml (1.75 mmol) of titanium tert-butoxide and 0.1 ml of acetic acid. The reaction mixture is heated at 100° C. for 2 hours, cooled, poured into water and stirred vigorously. The suspension is filtered through Celite, the filter bed being rinsed thoroughly with ethyl acetate. The phases of the filtrate are separated and extraction is carried out again with ethyl acetate. The extracts are washed with saturated sodium chloride solution and dried over sodium sulphate and the solvent is removed in vacuo to give 539 mg of (5-{[(2R,4R)-4-(3-chloro-4-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)hexylidene]amino}quinolin-2(1H)-one as a crude product. The imine is dissolved in 44 ml of CH2Cl2 and the solution is cooled to −30° C. 8.9 ml (8.9 mmol) of a 1M BBr3 solution in dichloromethane are added slowly dropwise over 15 minutes and the mixture is allowed to warm to room temperature over 22 hours. The reaction solution is poured onto a mixture of saturated NaHCO3 solution and ice. It is extracted repeatedly with ethyl acetate and the extracts are washed with saturated NaCl solution and dried over Na2SO4. Purification by column chromatography on silica gel (hexane/ethyl acetate 0-100%) yields 134 mg of the title compound.

後処理

  1. temperatureto warm to room temperature over 22 hours
  2. extractionIt is extracted repeatedly with ethyl acetate
  3. washthe extracts are washed with saturated NaCl solution
  4. dry with materialdried over Na2SO4
  5. customPurification by column chromatography on silica gel (hexane/ethyl acetate 0-100%)

出典と根拠

ORDレコード
ord-0517945fe9db43ee91839e3c0b4f91f3
出典データセット
uspto-grants-2011_02
特許番号
US07880042B2

反応ノート

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