Nitrogen → 1-[4-Chloro-6-(2,6-difluoropyridin-4-yl)-5-methylbiphenyl-2-yl]ethanone

HRID 510856

반응식

HRID 510856 반응식
Br[C:2]1[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[C:6]([C:14](=[O:16])[CH3:15])[CH:5]=[C:4]([Cl:17])[C:3]=1[CH3:18].[F:19][C:20]1[CH:25]=[C:24](B(O)O)[CH:23]=[C:22]([F:29])[N:21]=1.O.N#N>O1CCOCC1.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>[Cl:17][C:4]1[C:3]([CH3:18])=[C:2]([C:24]2[CH:23]=[C:22]([F:29])[N:21]=[C:20]([F:19])[CH:25]=2)[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[C:6]([C:14](=[O:16])[CH3:15])[CH:5]=1

참가 물질

8

반응물 4

HCID 947NitrogenHCID 962WaterHCID 27627472,6-Difluoropyridine-4-boronic acidHCID 866667871-(6-Bromo-4-chloro-5-methylbiphenyl-2-yl)ethanone

생성물 1

HCID 866667881-[4-Chloro-6-(2,6-difluoropyridin-4-yl)-5-methylbiphenyl-2-yl]ethanone수율 30%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 10340Sodium Carbonate용매HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

A biphasic solution of 1-(6-bromo-4-chloro-5-methylbiphenyl-2-yl)ethanone (0.20 g, 0.62 mmol) and (2,6-difluoropyridin-4-yl)boronic acid (0.12 g, 0.74 mmol) in 1,4-dioxane (2.0 mL) and 10% Na2CO3 in water (0.98 mL, 0.93 mmol)) was bubbled with N2 to degas. After tetrakis(triphenylphosphine)palladium(0) (29 mg, 0.025 mmol) was added the mixture was bubbled with N2 for 5 min. and heated at 100° C. overnight. The mixture was cooled to room temperature and diluted with ethyl acetate. The layers were separated and the aq. layer was extracted with more ethyl acetate. The combined extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified on silica gel column, eluting with 0-30% of ethyl acetate in hexane, to give the desired product (60 mg, 30%). LCMS calculated for C20H15ClF2NO (M+H)+: m/z=358.1. found: 358.0.

후처리

  1. customto degas
  2. customwas bubbled with N2 for 5 min.
  3. temperatureThe mixture was cooled to room temperature
  4. additiondiluted with ethyl acetate
  5. customThe layers were separated
  6. extractionthe aq. layer was extracted with more ethyl acetate
  7. washThe combined extracts were washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified on silica gel column
  12. washeluting with 0-30% of ethyl acetate in hexane

출처 및 근거

ORD 기록
ord-5c02a9856bba4c47b9bc7ab66ea54f41
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09096600B2

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