Cesium fluoride → 2-Cyclopropylmethoxy-5-(1-ethoxyvinyl)pyrimidine

HRID 633732Notes

Reaction equation

HRID 633732 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([O:8][CH2:9][CH:10]2[CH2:12][CH2:11]2)=[N:6][CH:7]=1.C([Sn](CCCC)(CCCC)[C:18]([O:20][CH2:21][CH3:22])=[CH2:19])CCC.[F-].[Cs+]>O1CCOCC1.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>[CH:10]1([CH2:9][O:8][C:5]2[N:4]=[CH:3][C:2]([C:18]([O:20][CH2:21][CH3:22])=[CH2:19])=[CH:7][N:6]=2)[CH2:12][CH2:11]1

Participants

6

Reactant 3

HCID 25953Cesium fluorideHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 638684135-Bromo-2-(cyclopropylmethoxy)pyrimidine

Product 1

HCID 1181998532-Cyclopropylmethoxy-5-(1-ethoxyvinyl)pyrimidineYield 65.6%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

760 mg (3.32 mmol) of 5-bromo-2-cyclopropylmethoxypyrimidine in 15 mL of dioxane, 1.36 mL (3.82 mmol) of tributyl(1-ethoxyvinyl)tin, 58.22 mg (0.08 mmol) of bis(triphenylphosphine)palladium(II) chloride, 1.12 g (7.30 mmol) of cesium fluoride. This mixture is subjected to microwave irradiation at 110° C. for 1 hour. The reaction mixture is evaporated to dryness and the residue is taken up in 100 mL of ethyl ether. A solution of 2.80 g of cesium fluoride in 10 mL of water is added. After stirring for 1 hour at room temperature, the mixture is filtered through Celite. The filtrate is washed with aqueous NaHCO3 solution and then with saturated NaCl solution. The organic phase is dried over magnesium sulfate and evaporated to dryness. The residue is purified by chromatography on silica gel (eluent: 10/90 EtOAc/heptane) to give 480 mg of 2-cyclopropylmethoxy-5-(1-ethoxyvinyl)pyrimidine, the characteristics of which are as follows:

Workup

  1. customirradiation at 110° C. for 1 hour
  2. customThe reaction mixture is evaporated to dryness
  3. additionA solution of 2.80 g of cesium fluoride in 10 mL of water is added
  4. filtrationthe mixture is filtered through Celite
  5. washThe filtrate is washed with aqueous NaHCO3 solution
  6. dry with materialThe organic phase is dried over magnesium sulfate
  7. customevaporated to dryness
  8. customThe residue is purified by chromatography on silica gel (eluent: 10/90 EtOAc/heptane)

Sources & evidence

ORD record
ord-e7ce809c36014d278ad07d9a7afe81da
Source dataset
uspto-grants-2016_04
Patent number
US09321790B2

Reaction notes

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