Triphenylphosphine → 3-amino-4-cyano-N-[2,6-dimethyl-4-(1-trifluoromethyl-vinyl)-phenyl]-benzamide

HRID 883056노트

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HRID 883056 반응식
[NH2:1][C:2]1[CH:3]=[C:4]([CH:25]=[CH:26][C:27]=1[C:28]#[N:29])[C:5]([NH:7][C:8]1[C:13]([CH3:14])=[CH:12][C:11](B2OC(C)(C)C(C)(C)O2)=[CH:10][C:9]=1[CH3:24])=[O:6].Br[C:31]([C:33]([F:36])([F:35])[F:34])=[CH2:32].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[OH-].[Na+]>COCCOC.O1CCCC1.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[NH2:1][C:2]1[CH:3]=[C:4]([CH:25]=[CH:26][C:27]=1[C:28]#[N:29])[C:5]([NH:7][C:8]1[C:13]([CH3:14])=[CH:12][C:11]([C:31]([C:33]([F:36])([F:35])[F:34])=[CH2:32])=[CH:10][C:9]=1[CH3:24])=[O:6]

참가 물질

8

반응물 4

HCID 11776TriphenylphosphineHCID 14798Sodium HydroxideHCID 2726961-Propene, 2-bromo-3,3,3-trifluoro-HCID 594559053-Amino-4-cyano-N-[2,6-dimethyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-benzamide

생성물 1

HCID 594559073-amino-4-cyano-N-[2,6-dimethyl-4-(1-trifluoromethyl-vinyl)-phenyl]-benzamide수율 81.3%

시약·촉매·용매 3

HCID 6102075Dichlorobis(triphenylphosphine)palladium촉매HCID 8028Tetrahydrofuran용매HCID 80711,2-Dimethoxyethane용매

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온도
130 °C

실험 절차

3-Amino-4-cyano-N-[2,6-dimethyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-benzamide (6 g, 15.3 mmol) (Example I4) was dissolved in a mixture of 1,2-dimethoxyethane (22 ml) and tetrahydrofuran (22 ml) in a microwave vial. Then, at 0° C. under an argon atmosphere, 2-bromo-3,3,3-trifluoro-propene (3.20 ml, 30.6 mmol), bis(triphenylphosphine) palladium(II) dichloride (PdCl2(PPh3)2) (0.32 g, 0.46 mmol) and triphenylphosphine (0.6 g, 2.29 mmol) were added. Finally, an aqueous solution of sodium hydroxide (2M) (30 ml) was added at 0° C. under an argon atmosphere. The vial was sealed and heated to 130° C. for 10 minutes in a microwave oven. The reaction mixture was allowed to cool to ambient temperature and concentrated. The residue was suspended in ethyl acetate (500 ml) and filtered through a plug of Celite®. The filtrate was washed twice with water (500 ml). The aqueous phases were extracted with ethyl acetate (500 ml). The combined organic phases were dried over sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel (eluent: cyclohexane/ethyl acetate 2:1) to give 3-amino-4-cyano-N-[2,6-dimethyl-4-(1-trifluoromethyl-vinyl)-phenyl]-benzamide (4.47 g, 81% yield) which was used without further purification. LC/MS (Method A): 360 (MH+); RT: 1.82.

후처리

  1. customThe vial was sealed
  2. temperatureto cool to ambient temperature
  3. concentrationconcentrated
  4. filtrationfiltered through a plug of Celite®
  5. washThe filtrate was washed twice with water (500 ml)
  6. extractionThe aqueous phases were extracted with ethyl acetate (500 ml)
  7. dry with materialThe combined organic phases were dried over sodium sulfate
  8. concentrationconcentrated
  9. customThe residue was purified by column chromatography on silica gel (eluent: cyclohexane/ethyl acetate 2:1)

출처 및 근거

ORD 기록
ord-3a5868ebc1b84c3daa491e1a780630d6
출처 데이터셋
uspto-grants-2012_08
특허 번호
US08236828B2

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