Sodium Carbonate → 4-Chloro-6-(3-thienyl)pyrimidine

HRID 1172345Notes

Reaction equation

HRID 1172345 reaction equation
[S:1]1[CH:5]=[CH:4][C:3](B(O)O)=[CH:2]1.[Cl:9][C:10]1[CH:15]=[C:14](Cl)[N:13]=[CH:12][N:11]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[Cl:9][C:10]1[CH:15]=[C:14]([C:3]2[CH:4]=[CH:5][S:1][CH:2]=2)[N:13]=[CH:12][N:11]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 709434,6-DichloropyrimidineHCID 581760Thiophene-3-boronic acid

Product 1

HCID 575389514-Chloro-6-(3-thienyl)pyrimidineYield 46%

Reagents, catalysts & solvents 1

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalyst

Conditions

Temperature
130 °C

Procedure

Thiophene-3-boronic acid (2.6 g, 20 mmol) was combined with 4,6-dichloropyrimidine (3.6 g, 24 mmol, 1.2 eq), bis(triphenylphosphine)palladium(II)dichloride (200 mg), and 3.0 g sodium carbonate in a resealable pressure flask. Sixty mL of a mixed solvent (N,N-dimethyl formamide/dimethyl ether/methanol/water 1:1:0.3:0.4 mL) was added, and the solution was purged with nitrogen prior to sealing. The reaction mixture was heated at 130° C. for three hours. The crude reaction mixture was cooled, partitioned between water and ethyl acetate. The organic material was washed with brine and dried over sodium sulfate. After concentrating to half-volume in vacuo, the resultant slurry was allowed to stand overnight, and then filtered to collect a white solid, which was washed with a small volume of ethyl acetate. The combined organic filtrates were chromatographed on silica gel (eluting with a gradient of 0%->5%->20% ethyl acetate in hexanes) to produce a second crop of solid material. The combined yield for the two batches was 1.83 g (46% yield).

Workup

  1. customthe solution was purged with nitrogen
  2. customThe crude reaction mixture
  3. temperaturewas cooled
  4. custompartitioned between water and ethyl acetate
  5. washThe organic material was washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationAfter concentrating to half-volume in vacuo
  8. filtrationfiltered
  9. customto collect a white solid, which
  10. washwas washed with a small volume of ethyl acetate
  11. customThe combined organic filtrates were chromatographed on silica gel (
  12. washeluting with a gradient of 0%->5%->20% ethyl acetate in hexanes)
  13. customto produce a second crop of solid material
  14. customThe combined yield for the two batches

Sources & evidence

ORD record
ord-d83aff4fc02240d6a764804497f2e47c
Source dataset
uspto-grants-2010_11
Patent number
US07834012B2

Reaction notes

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