Potassium Phosphate, Tribasic → 2-Fluoro-3-[4-methyl-2-(morpholin-4-yl)pyrimidin-5-yl]benzaldehyde

HRID 1021273Notes

Reaction equation

HRID 1021273 reaction equation
Br[C:2]1[C:3]([CH3:14])=[N:4][C:5]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[N:6][CH:7]=1.[F:15][C:16]1[C:21]([CH:22]=[O:23])=[CH:20][CH:19]=[CH:18][C:17]=1B(O)O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C(Cl)(Cl)Cl.C1(C)C=CC=CC=1>[F:15][C:16]1[C:17]([C:2]2[C:3]([CH3:14])=[N:4][C:5]([N:8]3[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)=[N:6][CH:7]=2)=[CH:18][CH:19]=[CH:20][C:21]=1[CH:22]=[O:23]

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, Tribasic2×HCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl2×HCID 162178292-Fluoro-3-formylphenylboronic Acid (contains varying amounts of Anhydride)2×HCID 683089314-(5-Bromo-4-methylpyrimidin-2-yl)morpholine

Product 1

HCID 866862302-Fluoro-3-[4-methyl-2-(morpholin-4-yl)pyrimidin-5-yl]benzaldehydeYield 64.9%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalyst2×HCID 962WaterSolvent3×HCID 1140TolueneSolventHCID 6212ChloroformSolvent

Conditions

Temperature
100 °C

Procedure

4-(5-Bromo-4-methylpyrimidin-2-yl)morpholine (372 mg), (2-fluoro-3-formylphenyl)boronic acid (315 mg), and potassium phosphate (918 mg) were mixed with toluene (10 ml) and water (10 ml), and palladium acetate (16 mg) and dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (59 mg) were added thereto, followed by stirring at 100° C. for 4 hours. (2-Fluoro-3-formylphenyl)boronic acid (315 mg), potassium phosphate (918 mg), palladium acetate (16 mg), dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (59 mg), and water (1 ml) were added to the reaction mixture, followed by stirring at 100° C. overnight. The reaction mixture was cooled to room temperature, CHCl3 and water were then added thereto, and the insoluble matter was removed by filtration. The organic layer of the filtrate was washed with water and saturated brine, dried over Na2SO4, and then concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (EtOAc/hexane/CHCl3) to obtain 2-fluoro-3-[4-methyl-2-(morpholin-4-yl)pyrimidin-5-yl]benzaldehyde (282 mg).

Workup

  1. additionwere added
  2. stirringby stirring at 100° C. overnight
  3. temperatureThe reaction mixture was cooled to room temperature
  4. customthe insoluble matter was removed by filtration
  5. washThe organic layer of the filtrate was washed with water and saturated brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customThe obtained residue was purified by silica gel column chromatography (EtOAc/hexane/CHCl3)

Sources & evidence

ORD record
ord-1d839fae0c15404f884fcf6ca5528707
Source dataset
uspto-grants-2014_05
Patent number
US08716470B2

Reaction notes

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