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

HRID 1398350노트

반응식

HRID 1398350 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), sodium carbonate (5.95 g, 56.1 mmol) solution in 7 mL of water and tetrakis(triphenylphosphine)palladium (0.973 g, 0.842 mmol) in a mixture of Toluene (50 mL) and Ethanol (8 mL), nitrogen gas was bubbled for 5 min. The reaction mixture was heated at 85° C. for 14 hours. After the completion, the reaction was diluted with EtOAc (50 mL), filtered through diatomaceous earth (Celite®). The filtrate was diluted with water and the organic layer was separated, washed with brine solution, dried over sodium sulfate. The organics were concentrated under reduced pressure and residue so obtained was purified by comb flash column 120 g using hexane/ethyl acetate. Product eluted at 30% EtOAc 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. LC/MS (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=11.20, 17.60 Hz, 1H), 5.99 (dd, J=0.80, 17.60 Hz, 1H), 5.47 (dd, J=0.80, 11.40 Hz, 1H), 2.12 (s, 3H).

후처리

  1. customwas bubbled for 5 min
  2. additionAfter the completion, the reaction was diluted with EtOAc (50 mL)
  3. filtrationfiltered through diatomaceous earth (Celite®)
  4. additionThe filtrate was diluted with water
  5. customthe organic layer was separated
  6. washwashed with brine solution
  7. dry with materialdried over sodium sulfate
  8. concentrationThe organics were concentrated under reduced pressure and residue
  9. customso obtained
  10. customwas purified by comb flash column 120 g
  11. washProduct eluted at 30% EtOAc in hexane
  12. concentrationrequired fractions were concentrated

출처 및 근거

ORD 기록
ord-ebe78c3a09c34247994bda67a4cba64b
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08901305B2

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