Potassium Phosphate, Tribasic → 1-(5-(3-(Trifluoromethyl)phenyl)pyrimidin-2-yl)ethanone

HRID 57395

Reaction equation

HRID 57395 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([C:8](=[O:10])[CH3:9])=[N:6][CH:7]=1.[F:11][C:12]([F:23])([F:22])[C:13]1[CH:14]=[C:15](B(O)O)[CH:16]=[CH:17][CH:18]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CN(C1C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=CC=CC=1)C>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[F:11][C:12]([F:23])([F:22])[C:13]1[CH:18]=[C:17]([C:2]2[CH:3]=[N:4][C:5]([C:8](=[O:10])[CH3:9])=[N:6][CH:7]=2)[CH:16]=[CH:15][CH:14]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 27343883-(Trifluoromethyl)phenylboronic acidHCID 534880641-(5-Bromopyrimidin-2-yl)ethan-1-one

Product 1

HCID 867301721-(5-(3-(Trifluoromethyl)phenyl)pyrimidin-2-yl)ethanoneYield 65.5%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Procedure

A cloudy solution of 1-(5-bromopyrimidin-2-yl)ethanone (300 mg, 1.49 mmol), 3-(trifluoromethyl)phenylboronic acid (567 mg, 2.98 mmol), K3PO4 (950 mg, 4.48 mmol), DavePhos ligand [2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl](59 mg, 0.15 mmol), and Pd(OAc)2 (17 mg, 0.075 mmol) in 6 mL toluene was heated at 100° C. for 1 h. The mixture was cooled to room temperature, and filtered through Celite. Filter cake was rinsed with 30 mL EtOAc. The filtrate was poured into 20 mL water. Layers were separated, and the aqueous was further extracted with EtOAc (20 mL). Combined organics were washed with water (20 mL) and brine (20 mL), dried over Na2SO4, filtered and concentrated directly onto silica gel. Column chromatography (10-100% EtOAc/heptane) gave 0.26 g 1-(5-(3-(trifluoromethyl)phenyl)pyrimidin-2-yl)ethanone as tan solid. MS m/z 267.1 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 9.16 (s, 2H), 7.93-7.69 (m, 4H), 2.87 (s, 3H).

Workup

  1. filtrationfiltered through Celite
  2. filtrationFilter cake
  3. washwas rinsed with 30 mL EtOAc
  4. additionThe filtrate was poured into 20 mL water
  5. customLayers were separated
  6. extractionthe aqueous was further extracted with EtOAc (20 mL)
  7. washCombined organics were washed with water (20 mL) and brine (20 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated directly onto silica gel

Sources & evidence

ORD record
ord-1308a2f6995e48148fcbb0c8db6844bd
Source dataset
uspto-grants-2016_09
Patent number
US09434719B2

Linked notes

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