Potassium Carbonate → HCID 79072851, compound

HRID 1184408Notes

Reaction equation

HRID 1184408 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([F:9])=[CH:4][N:3]=1.[Cl:10][C:11]1[CH:16]=[CH:15][C:14](B(O)O)=[CH:13][CH:12]=1.C(=O)([O-])[O-].[K+].[K+].B(O)O>O1CCCC1.O.C(OCC)(=O)C.C1(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)C=CC=CC=1>[Cl:1][C:2]1[N:7]=[C:6]([C:14]2[CH:15]=[CH:16][C:11]([Cl:10])=[CH:12][CH:13]=2)[C:5]([F:9])=[CH:4][N:3]=1

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 61668Boronic AcidHCID 742994-Chlorophenylboronic acidHCID 2507052,4-Dichloro-5-fluoropyrimidine

Product 1

HCID 79072851HCID 79072851, compoundYield 13.7%

Reagents, catalysts & solvents 4

HCID 178420554HCID 178420554, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 5.00 g 2,4-dichloro-5-fluoropyrimidine, 4.683 g p-chlorophenylboronic acid, 1.730 g tetrakistriphenylphosphino palladium and 8.278 g potassium carbonate in 125 ml tetrahydrofurane and 125 ml water was heated to reflux for 3 h. The reaction mixture was cooled to room temperature and diluted with ethyl acetate. The phases were separated and the organic phase was washed with brine dried over sodium sulfate and evaporated. The solid residue was triturated in ca 60 ml methanol for 30 min. The solids were collected by filtration to yield 5.2 g of an off white solid (contains some boronic acid which gives a start spot). The mother liquor was evaporated and the residue was purified by chromatography on silica gel with heptane:ethyl acetate=8:2 to 1:1 to yield 1.0 g of the product as white solid. Both crops were combined and dissolved in ca 50 ml dichloromethane and filtered over ca 50 g silica gel with dichloromethane to remove a polar start spot. The filtrate was concentrated under aspirator vacuum whereby precipitation occurred. The solid was collected by filtration to yield 5.76 g of the title compound as white crystals. MS (EI): 230.1 and 228.1 (M+H).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 3 h
  3. customThe phases were separated
  4. washthe organic phase was washed with brine
  5. dry with materialdried over sodium sulfate
  6. customevaporated
  7. customThe solid residue was triturated in ca 60 ml methanol for 30 min
  8. filtrationThe solids were collected by filtration
  9. customto yield 5.2 g of an off white solid (
  10. customgives a start spot)
  11. customThe mother liquor was evaporated
  12. customthe residue was purified by chromatography on silica gel with heptane

Sources & evidence

ORD record
ord-f53d23cc948a4bb38832a0ce922082fe
Source dataset
uspto-grants-2014_03
Patent number
US08669254B2

Reaction notes

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