Sodium Carbonate → 2-(5-(Tert-butyl)-2-(methoxymethoxy)phenyl)-5-(trifluoromethyl)pyrimidine

HRID 1480627Notes

Reaction equation

HRID 1480627 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][N:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[C:18]([C:22]1[CH:23]=[CH:24][C:25]([O:31][CH2:32][O:33][CH3:34])=[C:26](B(O)O)[CH:27]=1)([CH3:21])([CH3:20])[CH3:19]>C(COC)OC.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>[C:18]([C:22]1[CH:27]=[CH:26][C:25]([O:31][CH2:32][O:33][CH3:34])=[C:24]([C:2]2[N:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][N:3]=2)[CH:23]=1)([CH3:21])([CH3:19])[CH3:20]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 133170192-Chloro-5-(trifluoromethyl)pyrimidineHCID 86718588[5-Tert-butyl-2-(methoxymethoxy)phenyl]boronic acid

Product 1

HCID 867185892-(5-(Tert-butyl)-2-(methoxymethoxy)phenyl)-5-(trifluoromethyl)pyrimidineYield 44.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 2-chloro-5-(trifluoromethyl)pyrimidine (0.300 g, 1.64 mmol) in dimethoxyethane (9 mL) was added a 2 M aqueous solution of sodium carbonate (3.7 mL, 7.4 mmol) and (5-(tert-butyl)-2-(methoxymethoxy)phenyl)boronic acid (0.500 g, 2.14 mmol). The solution was degassed with nitrogen for five minutes and tetrakis(triphenylphosphine)palladium(0) (95 mg, 0.082 mmol) was added and the reaction mixture heated to 80° C. in a sealed vial for 16 hours. The cooled reaction mixture was partitioned between ethyl acetate (25 mL) and 1 M aqueous sodium hydroxide solution (25 mL), the organic phase separated, dried (Na2SO4), filtered and concentrated under reduced pressure to give a yellow syrup. The crude product was purified by chromatography on silica eluting with a solvent gradient of 0 to 100% ethyl acetate in hexanes to give 2-(5-(tert-butyl)-2-(methoxymethoxy)phenyl)-5-(trifluoromethyl)pyrimidine (0.25 g, 44% yield) as a colorless oil.

Workup

  1. customThe solution was degassed with nitrogen for five minutes
  2. customThe cooled reaction mixture
  3. customwas partitioned between ethyl acetate (25 mL) and 1 M aqueous sodium hydroxide solution (25 mL)
  4. customthe organic phase separated
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto give a yellow syrup
  9. customThe crude product was purified by chromatography on silica eluting with a solvent gradient of 0 to 100% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-0af310e8b08d486e8c72a3c43bb1ac7b
Source dataset
uspto-grants-2016_08
Patent number
US09409893B2

Reaction notes

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