Potassium Carbonate → 2-(2,6-Diethyl-phenyl)-4-methoxy-6-methyl-pyrimidine-5-carboxylic acid methyl ester

HRID 1091947Notes

Reaction equation

HRID 1091947 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:6]([O:13][CH3:14])=[N:7][C:8](Cl)=[N:9][C:10]=1[CH3:11])=[O:4].C(=O)([O-])[O-].[K+].[K+].[CH2:21]([C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([CH2:29][CH3:30])[C:24]=1B(O)O)[CH3:22]>COCCOC.O>[CH3:1][O:2][C:3]([C:5]1[C:6]([O:13][CH3:14])=[N:7][C:8]([C:24]2[C:25]([CH2:29][CH3:30])=[CH:26][CH:27]=[CH:28][C:23]=2[CH2:21][CH3:22])=[N:9][C:10]=1[CH3:11])=[O:4]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 18437832(2,6-Diethylphenyl)boronic acidHCID 575314302-Chloro-4-methoxy-6-methyl-pyrimidine-5-carboxylic acid methyl ester

Product 1

HCID 575315802-(2,6-Diethyl-phenyl)-4-methoxy-6-methyl-pyrimidine-5-carboxylic acid methyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
95 °C

Procedure

To a solution of 2-chloro-4-methoxy-6-methyl-pyrimidine-5-carboxylic acid methyl ester (4.1 g, 19.0 mmol) in DME (100 mL) is added potassium carbonate (10.5 g, 76 mmol, 4 eq) in water (40 mL) followed by 2,6-diethylphenylboronic acid (6.77 g, 38 mmol, 2 eq). The resulting mixture is degassed by bubbling with argon for 20 min. Pd(PPh3)4 (5 mol %) is added and the resulting yellow biphasic solution is heated at 95° C. in a sealed tube with magnetic stirring for 18 h. The reaction mixture is cooled to room temperature, diluted with water (100 mL) and extracted with EtOAc (75 mL×3). The combined organic layers are washed with brine (75 mL), dried over magnesium sulfate, filtered and evaporated at reduced pressure. The resulting orange oil is purified by chromatography on silica gel (1:2 ether/hexanes) to afford the title compound as a colorless oil. 1H NMR (CDCl3) δ=7.29 (dd, 1H), 7.14 (d, 2H), 4.00 (s, 3H), 3. 98 (s, 3H), 2.55 (s, 3H), 2.39 (q, 4H), 1.10 (t, 6H).

Workup

  1. customThe resulting mixture is degassed
  2. customby bubbling with argon for 20 min
  3. additionPd(PPh3)4 (5 mol %) is added
  4. temperatureThe reaction mixture is cooled to room temperature
  5. additiondiluted with water (100 mL)
  6. extractionextracted with EtOAc (75 mL×3)
  7. washThe combined organic layers are washed with brine (75 mL)
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. customevaporated at reduced pressure
  11. customThe resulting orange oil is purified by chromatography on silica gel (1:2 ether/hexanes)

Sources & evidence

ORD record
ord-4d9a1f3009c4446b9c3cca6a92cb6d61
Source dataset
uspto-grants-2012_03
Patent number
US08129395B2

Reaction notes

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