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

HRID 598229노트

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HRID 598229 반응식
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

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 178418807HCID 178418807, 화합물촉매HCID 1140Toluene용매HCID 6228Dimethylformamide용매

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온도
90 °C

실험 절차

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)+.

후처리

  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)

출처 및 근거

ORD 기록
ord-91b6ce6bbb7d41f8b1d8ad9c9ca986c8
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07897621B2

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