Sodium Carbonate → 4-(4-Fluorophenyl)-7-methyl-2-quinolinecarbonitrile

HRID 922750노트

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HRID 922750 반응식
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([CH3:12])=[CH:9][CH:10]=2)[N:5]=[C:4]([C:13]#[N:14])[CH:3]=1.[F:15][C:16]1[CH:21]=[CH:20][C:19](B(O)O)=[CH:18][CH:17]=1.C([O-])([O-])=O.[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCOCC1>[F:15][C:16]1[CH:21]=[CH:20][C:19]([C:2]2[C:11]3[C:6](=[CH:7][C:8]([CH3:12])=[CH:9][CH:10]=3)[N:5]=[C:4]([C:13]#[N:14])[CH:3]=2)=[CH:18][CH:17]=1

참가 물질

6

반응물 3

HCID 10340Sodium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 597749194-Chloro-7-methylquinoline-2-carbonitrile

생성물 1

HCID 574378434-(4-Fluorophenyl)-7-methyl-2-quinolinecarbonitrile수율 85.9%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

4-Chloro-7-methylquinoline-2-carbonitrile (1-5, 2.47 g, 12.2 mmol, 1.0 equiv.), 4-fluorophenylboronic acid (2.05 g, 14.63 mmol, 1.2 equiv.), Pd(PPh3)4 (0.7 g, 0.61 mmol, 0.05 equiv), and 1M aqueous Na2CO3 (12.2 ml, 2.39 mmol) was added into 1,4-dioxane (40 mL). The mixture was degassed and stirred at 100° C. for 16 hours, until disappearance of the starting material. The mixture was cooled, saturated aqueous sodium hydrogen carbonate (2 mL) was added and the mixture was extracted with ethyl acetate (2×50 mL). The combined organic fractions were washed with brine, dried (MgSO4), filtered and the solvent was evaporated under reduced pressure. The residue was treated with 50 ml of MeOH, stirred vigorously at rt for 1 h, the mixture was filtered and washed with MeOH. The solid was collected and dried under vacuum. The filtrate was concentrated and retreated with MeOH to get a second crop of white solid that was combined to the first to give 2.75 g of 4-(4-fluorophenyl)-7-methylquinoline-2-carbonitrile (1-6). LRMS m/z (M+H)+ 263.3 found, 263.3 required.

후처리

  1. customThe mixture was degassed
  2. temperatureThe mixture was cooled
  3. additionsaturated aqueous sodium hydrogen carbonate (2 mL) was added
  4. extractionthe mixture was extracted with ethyl acetate (2×50 mL)
  5. washThe combined organic fractions were washed with brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customthe solvent was evaporated under reduced pressure
  9. additionThe residue was treated with 50 ml of MeOH
  10. stirringstirred vigorously at rt for 1 h
  11. filtrationthe mixture was filtered
  12. washwashed with MeOH
  13. customThe solid was collected
  14. customdried under vacuum
  15. concentrationThe filtrate was concentrated
  16. customto get a second crop of white solid

출처 및 근거

ORD 기록
ord-1fa4a12661894ea8a84d8cd447818399
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09278960B2

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