Tributylvinyltin → HCID 73672882, compound

HRID 1051195Notes

Reaction equation

HRID 1051195 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([F:9])=[CH:4][N:3]=1.[CH2:10]([Sn](CCCC)(CCCC)C=C)[CH2:11]CC.[F-].[K+]>ClCCl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:1][C:2]1[N:7]=[C:6]([CH:10]=[CH2:11])[C:5]([F:9])=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 81998TributylvinyltinHCID 2507052,4-Dichloro-5-fluoropyrimidineHCID 522689Potassium Fluoride

Product 1

HCID 73672882HCID 73672882, compoundYield 77%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of 2,4-dichloro-5-fluoropyrimidine (5.0 g, 30.0 mmol, 1.0 equiv), tributyl(vinyl)tin (10.4 g, 33.0 mmol, 1.1 equiv) in dichloromethane (50 mL) was degassed with a stream of nitrogen for 10 minutes. Bis(triphenylphosphine)palladium(II) chloride (0.53 g, 0.75 mmol, 0.025 equiv) was added. The resulting mixture was degassed with a stream of nitrogen for an additional 15 minutes and heated at reflux for 24 hours. The reaction mixture was cooled to room temperature and quenched with an aqueous potassium fluoride solution (2 M, 75 mL, 5 equiv). The resulting mixture was allowed to stir for 2 hours and filtered through Celite®. The filtrate was poured into a separatory funnel and separated. The organic layer was washed with water (20 mL) and saturated brine (20 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure at 20° C. The resulting crude product was purified on an AnaLogix® (SF40-115 g) column. The gradient utilized for the purification was 10 minutes isocratic pentane, followed by a 20 minutes ramp to 5% diethyl ether in pentane. The pure fractions were combined and concentrated under reduced pressure at 20° C. to give 2-chloro-5-fluoro-4-vinylpyrimidine as an oil (3.65 g, 77% yield).

Workup

  1. customwas degassed with a stream of nitrogen for 10 minutes
  2. customThe resulting mixture was degassed with a stream of nitrogen for an additional 15 minutes
  3. temperatureheated
  4. temperatureat reflux for 24 hours
  5. filtrationfiltered through Celite®
  6. additionThe filtrate was poured into a separatory funnel
  7. customseparated
  8. washThe organic layer was washed with water (20 mL) and saturated brine (20 mL)
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure at 20° C
  12. customThe resulting crude product was purified on an AnaLogix® (SF40-115 g) column
  13. customThe gradient utilized for the purification
  14. waitwas 10 minutes
  15. waitisocratic pentane, followed by a 20 minutes ramp to 5% diethyl ether in pentane
  16. concentrationconcentrated under reduced pressure at 20° C.

Sources & evidence

ORD record
ord-972dc73ad41f4a7e858fdcddbce3039e
Source dataset
uspto-grants-2016_07
Patent number
US09388167B2

Reaction notes

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