Potassium Carbonate → 2-Chloro-4-methyl-6-phenylpyrimidine

HRID 1911842Notes

Reaction equation

HRID 1911842 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[C:4]([CH3:9])[N:3]=1.[C:10]1(B(O)O)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C([O-])([O-])=O.[K+].[K+]>C1(C)C=CC=CC=1.CO.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:1][C:2]1[N:3]=[C:4]([CH3:9])[CH:5]=[C:6]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[N:7]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 794712,4-Dichloro-6-methylpyrimidine

Product 1

HCID 6092722-Chloro-4-methyl-6-phenylpyrimidine

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 2,4-dichloro-6-methylpyrimidine (5 g, 30.7 mmol), benzeneboronic acid (3.74 g, 30.7 mmol), K2CO3 (12.72 g, 92 mmol) and Pd(PPh3)4 (1.06 g, 0.92 mmol) in toluene (150 ml) and methanol (35 ml) was degassed with nitrogen and heated at 90° C. overnight. The mixture was cooled and water (200 ml) added. The organic layer was separated and the aqueous extracted with EtOAc (×2). The organic layers were combined and dried over MgSO4, filtered and evaporated. The residue was purified by MPLC (Biotage Horizon: FLASH 40+M) eluent: 100% Hexanes (180 ml), gradient rising from 100% Hexanes to 20% EtOAc in Hexanes (1800 ml), then 20% EtOAc in Hexanes (1000 ml) to give 3 g (48%). 1H NMR (CDCl3): 2.61 (s, 3H), 7.52 (m, 4H), 8.08 (m, 2H).

Workup

  1. customwas degassed with nitrogen
  2. temperatureThe mixture was cooled
  3. additionwater (200 ml) added
  4. customThe organic layer was separated
  5. extractionthe aqueous extracted with EtOAc (×2)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by MPLC (Biotage Horizon: FLASH 40+M) eluent
  10. custom20% EtOAc in Hexanes (1000 ml) to give 3 g (48%)

Sources & evidence

ORD record
ord-3eca0d56127c4b8f87a67490df3cb027
Source dataset
uspto-grants-2013_12
Patent number
US08604038B2

Reaction notes

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