Pyridine → N-(4-chloro-5-vinylpyridin-2-yl)acetamide

HRID 2369529노트

반응식

HRID 2369529 반응식
Br[C:2]1[C:3]([Cl:12])=[CH:4][C:5]([NH:8][C:9](=[O:11])[CH3:10])=[N:6][CH:7]=1.N1C=CC=[CH:15][CH:14]=1.C(=O)([O-])[O-].[Na+].[Na+]>O.C1(C)C=CC=CC=1.C(O)C.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:12][C:3]1[C:2]([CH:14]=[CH2:15])=[CH:7][N:6]=[C:5]([NH:8][C:9](=[O:11])[CH3:10])[CH:4]=1

참가 물질

8

반응물 3

HCID 1049PyridineHCID 10340Sodium CarbonateHCID 86695929N-(5-bromo-4-chloropyridin-2-yl)acetamide

생성물 1

HCID 86695930N-(4-chloro-5-vinylpyridin-2-yl)acetamide수율 99%

시약·촉매·용매 4

HCID 178418397HCID 178418397, 화합물촉매HCID 702Ethanol용매HCID 962Water용매HCID 1140Toluene용매

반응 조건

온도
85 °C

실험 절차

To a stirred solution of N-(5-bromo-4-chloropyridin-2-yl)acetamide (7 g, 28.1 mmol), 2,4,6-trivinyl-1,3,5,2,4,6-trioxatriborinane complex with pyridine (1:1) (8.78 g, 36.5 mmol), and sodium carbonate (5.95 g, 56.1 mmol) solution in 7 mL of water in a mixture of toluene (50 mL) and ethanol (8 mL), was added Pd(PPh3)4 (0.973 g, 0.842 mmol). The solution was purged with nitrogen gas was bubbled for 5 min then heated at 85° C. for 14 h. The reaction was cooled to room temperature and was diluted with ethyl acetate (50 mL) ten filtered through a bed of celite. The filtrate was diluted with water and the organic layer was separated, washed with brine, dried over sodium sulphate. The organics were concentrated under reduced pressure and residue was purified by silica gel column chromatography using a gradient of ethyl acetate in hexanes. Product eluted at 30% ethyl acetate in hexane and required fractions were concentrated to yield N-(4-chloro-5-vinylpyridin-2-yl)acetamide (5.92 g, 27.7 mmol, 99% yield) as yellow solid. LCMS (ESI) m/e 197.2 [(M+H)+, calcd for C9H10ClN2O 197.04] LC/MS retention time (method A): tR=1.50 min; 1H NMR (400 MHz, DMSO-d6) δ 10.79 (s, 1H), 8.64 (s, 1H), 8.18 (d, J=6.40 Hz, 1H), 6.88 (dd, J=11.2, 17.6 Hz, 1H), 5.99 (dd, J=17.60, 0.80 Hz, 1H), 5.47 (dd, J=11.40, 0.80 Hz, 1H), 2.12 (s, 3H).

후처리

  1. customThe solution was purged with nitrogen gas
  2. customwas bubbled for 5 min
  3. temperatureThe reaction was cooled to room temperature
  4. additionwas diluted with ethyl acetate (50 mL) ten
  5. filtrationfiltered through a bed of celite
  6. additionThe filtrate was diluted with water
  7. customthe organic layer was separated
  8. washwashed with brine
  9. dry with materialdried over sodium sulphate
  10. concentrationThe organics were concentrated under reduced pressure and residue
  11. customwas purified by silica gel column chromatography
  12. washProduct eluted at 30% ethyl acetate in hexane
  13. concentrationrequired fractions were concentrated

출처 및 근거

ORD 기록
ord-f2348b2d94f54788bf56baceca115fef
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08703953B2

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