Nitrogen → 4-Chloro-6-(4-(trifluoromethyl)phenyl)pyrimidine

HRID 1914521Notes

Reaction equation

HRID 1914521 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6](Cl)[N:5]=[CH:4][N:3]=1.[F:9][C:10]([F:21])([F:20])[C:11]1[CH:16]=[CH:15][C:14](B(O)O)=[CH:13][CH:12]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].N#N>C(COC)OC.O.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[CH:7]=[C:6]([C:14]2[CH:15]=[CH:16][C:11]([C:10]([F:21])([F:20])[F:9])=[CH:12][CH:13]=2)[N:5]=[CH:4][N:3]=1

Participants

8

Reactant 4

HCID 947NitrogenHCID 62657Potassium Phosphate, TribasicHCID 709434,6-DichloropyrimidineHCID 27343894-(Trifluoromethyl)phenylboronic acid

Product 1

HCID 167478374-Chloro-6-(4-(trifluoromethyl)phenyl)pyrimidineYield 48%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

In a screw top flask, 4,6-dichloropyrimidine (3.1 g, 21 mmol), 4-trifluoromethyl-phenyl boronic acid (3.9 g, 21 mmol) and potassium phosphate (8.8 g, 42 mmol) were combined in dimethoxyethane (60 mL) and water (12 mL). The flask was flushed with N2 and tetrakis(triphenylphosphine)palladium (1.2 g, 1.0 mmol) was added. The flask was sealed and heated to 90° C. for 12 hours. The reaction mixture was cooled to rt and H2O (50 mL) was added and resulting mixture was extracted with EtOAc (3×50 mL). The organic phases were combined, washed with brine (50 mL), dried with Na2SO4, filtered, and concentrated. The resulting residue was purified by flash column chromatography using ethyl acetate-hexanes (0%-20%) to provide a clear oil (2.6 g, 48%). MS (ESI): mass calcd. for C11H6ClF3N2, 258.0; m/z found 259.1 [M+H]+.

Workup

  1. additionwas added
  2. customThe flask was sealed
  3. temperatureThe reaction mixture was cooled to rt
  4. customresulting mixture
  5. extractionwas extracted with EtOAc (3×50 mL)
  6. washwashed with brine (50 mL)
  7. dry with materialdried with Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resulting residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-a27c7a18630d4bb795540af2343595ba
Source dataset
uspto-grants-2013_12
Patent number
US08614201B2

Reaction notes

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