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

HRID 2369529Notes

Reaction equation

HRID 2369529 reaction equation
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

Participants

8

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
85 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-f2348b2d94f54788bf56baceca115fef
Source dataset
uspto-grants-2014_04
Patent number
US08703953B2

Reaction notes

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