Water → 5-(4-Chloro-phenyl)-N-(2-cyclopropyl-2-hydroxy-propyl)-6-(2,2,2-trifluoro-ethoxy)-2-trifluoromethyl-nicotinamide

HRID 598229ノート

反応式

HRID 598229 の反応式
Br[C:2]1[C:3]([O:22][CH2:23][C:24]([F:27])([F:26])[F:25])=[N:4][C:5]([C:18]([F:21])([F:20])[F:19])=[C:6]([CH:17]=1)[C:7]([NH:9][CH2:10][C:11]([CH:14]1[CH2:16][CH2:15]1)([OH:13])[CH3:12])=[O:8].[Cl:28][C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1.C(=O)([O-])[O-].[Na+].[Na+].O>C1(C)C=CC=CC=1.CN(C)C=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[Cl:28][C:29]1[CH:34]=[CH:33][C:32]([C:2]2[C:3]([O:22][CH2:23][C:24]([F:25])([F:26])[F:27])=[N:4][C:5]([C:18]([F:21])([F:20])[F:19])=[C:6]([CH:17]=2)[C:7]([NH:9][CH2:10][C:11]([CH:14]2[CH2:16][CH2:15]2)([OH:13])[CH3:12])=[O:8])=[CH:31][CH:30]=1

参加物

8

反応物 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 742994-Chlorophenylboronic acidHCID 866347985-Bromo-N-(2-cyclopropyl-2-hydroxy-propyl)-6-(2,2,2-trifluoro-ethoxy)-2-trifluoromethyl-nicotinamide

生成物 1

HCID 442406755-(4-Chloro-phenyl)-N-(2-cyclopropyl-2-hydroxy-propyl)-6-(2,2,2-trifluoro-ethoxy)-2-trifluoromethyl-nicotinamide収率 56.1%

試薬・触媒・溶媒 3

HCID 178418807HCID 178418807、化合物触媒HCID 1140Toluene溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
90 °C

実験手順

5-Bromo-N-(2-cyclopropyl-2-hydroxy-propyl)-6-(2,2,2-trifluoro-ethoxy)-2-trifluoromethyl-nicotinamide (0.09 g, 0.19 mmol) was dissolved in toluene (4 mL) and dimethylformamide (0.3 mL). To this solution was added with stirring [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) CH2Cl2 (8 mg, 0.010 mmol), 4-chlorophenylboronic acid (32 mg, 0.20 mmol) and sodium carbonate solution (2M, 0.20 mL). This mixture was heated to 90° C. for 15 h and cooled to room temperature. Water (10 mL) was added, the phases were separated and the water mixture was extracted with ethylacetate. Organic phases were pooled, dried with MgSO4 and the volatiles removed in vacuo. The residue was purified by flash chromatography (SiO2, dichloromethane/ethyl acetate) to give the title compound (53 mg) as a brown gum; MS (ISP) 497.2 (M)+.

後処理

  1. temperaturecooled to room temperature
  2. customthe phases were separated
  3. extractionthe water mixture was extracted with ethylacetate
  4. dry with materialdried with MgSO4
  5. customthe volatiles removed in vacuo
  6. customThe residue was purified by flash chromatography (SiO2, dichloromethane/ethyl acetate)

出典と根拠

ORDレコード
ord-91b6ce6bbb7d41f8b1d8ad9c9ca986c8
出典データセット
uspto-grants-2011_03
特許番号
US07897621B2

反応ノート

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