Sodium hydride → 7-({6-[4-(Trifluoromethyl)phenyl]pyrimidin-4-yl}oxy)quinoline

HRID 857615Notes

Reaction equation

HRID 857615 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=2)[N:5]=[CH:4][N:3]=1.[OH:18][C:19]1[CH:28]=[C:27]2[C:22]([CH:23]=[CH:24][CH:25]=[N:26]2)=[CH:21][CH:20]=1.[H-].[Na+]>CN(C=O)C>[F:15][C:14]([F:17])([F:16])[C:11]1[CH:12]=[CH:13][C:8]([C:6]2[N:5]=[CH:4][N:3]=[C:2]([O:18][C:19]3[CH:28]=[C:27]4[C:22]([CH:23]=[CH:24][CH:25]=[N:26]4)=[CH:21][CH:20]=3)[CH:7]=2)=[CH:9][CH:10]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 167478374-Chloro-6-(4-(trifluoromethyl)phenyl)pyrimidineHCID 1354268667-Hydroxyquinoline

Product 1

HCID 104290187-({6-[4-(Trifluoromethyl)phenyl]pyrimidin-4-yl}oxy)quinoline

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a 250-mL, round-bottomed flask containing 4-chloro-6-(4-trifluoromethyl-phenyl)-pyrimidine, (Example 2(a), Method A), (2.5 g, 9.7 mmol) and 7-hydroxyquinoline (2.0 g, 14 mmol, Acros) in DMF (30 mL), was added NaH (5.4 g, 14 mmol, 60% in mineral oil, Aldrich) at room temperature The solution was then stirred at room temperature for 4 h. After the solvent was removed in vacuum, EtOAc (100 mL) and water (50 mL) were added to the residue. The solid precipitate was filtered and the filtrate was poured into a separatory funnel. The organic layer was separated, combined with the previously isolated solid, concentrated in vacuum, and purified by silica gel chromatography (2:1 hexanes/EtOAc). The purified product was dissolved in acetone (30 mL) and MeOH (10 mL), and to the solution was added water (30 mL) in small portions. The precipitated solid was filtered, washed with water (5 mL), and dried under vacuum at 50° C. for 48 h to furnish the title compound as a white solid. Mp: 178–180° C. MS (ESI, pos. ion) m/z: 368 (M+1). Anal. Calcd for C20H12F3N3O: C, 65.40; H, 3.29; N, 11.44. Found: C, 65.42; H, 3.23; N, 11.43.

Workup

  1. customAfter the solvent was removed in vacuum, EtOAc (100 mL) and water (50 mL)
  2. additionwere added to the residue
  3. filtrationThe solid precipitate was filtered
  4. additionthe filtrate was poured into a separatory funnel
  5. customThe organic layer was separated
  6. concentrationconcentrated in vacuum
  7. custompurified by silica gel chromatography (2:1 hexanes/EtOAc)
  8. dissolutionThe purified product was dissolved in acetone (30 mL)
  9. additionMeOH (10 mL), and to the solution was added water (30 mL) in small portions
  10. filtrationThe precipitated solid was filtered
  11. washwashed with water (5 mL)
  12. customdried under vacuum at 50° C. for 48 h

Sources & evidence

ORD record
ord-cd56a4d2bb064126b080a21cce45c082
Source dataset
uspto-grants-2006_12
Patent number
US07144888B2

Reaction notes

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