Hydrochloric Acid → 3-[(2,3-Difluoro-6-nitrophenyl)oxy]-5-(methyloxy)benzonitrile

HRID 1875240Notes

Reaction equation

HRID 1875240 reaction equation
[H-].[Na+].[OH:3][C:4]1[CH:5]=[C:6]([CH:9]=[C:10]([O:12][CH3:13])[CH:11]=1)[C:7]#[N:8].[F:14][C:15]1[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[C:17](F)[C:16]=1[F:25].Cl>C1COCC1>[F:25][C:16]1[C:15]([F:14])=[CH:20][CH:19]=[C:18]([N+:21]([O-:23])=[O:22])[C:17]=1[O:3][C:4]1[CH:5]=[C:6]([CH:9]=[C:10]([O:12][CH3:13])[CH:11]=1)[C:7]#[N:8]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 698711,2,3-Trifluoro-4-nitrobenzeneHCID 229962023-Hydroxy-5-methoxybenzonitrile

Product 1

HCID 687222673-[(2,3-Difluoro-6-nitrophenyl)oxy]-5-(methyloxy)benzonitrileYield 92.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

NaH (2.05 g, 51.2 mmol) was added portionwise to a 0° C. solution of 3-hydroxy-5-(methyloxy)benzonitrile (7.63 g, 51.2 mmol) (prepared following the procedure in Magano et al. J. Org. Chem. 2006, 71, 7103) in THF (205 ml). When addition was complete, the thick suspension was stirred at this temperature for another 30 mins, and trifluoronitrobenzene (9.51 g, 53.7 mmol) was then added. The reaction mixture was stirred at RT for 3 h, dilute HCl was added and the solution was extracted with EtOAc. The organic layer was dried (Na2SO4), filtered, evaporated and purified by silica gel chromatography (0-30% EtOAc/hexanes) to afford the title compound (14.44 g, 92%) as a light yellow solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.96 (ddd, J=9.36, 4.97, 2.24 Hz, 1H) 7.28-7.35 (m, 1H) 6.95 (d, J=0.73 Hz, 1H) 6.78 (t, J=2.15 Hz, 1H) 6.73 (s, 1H) 3.85 (s, 3H).

Workup

  1. customprepared
  2. additionWhen addition
  3. stirringThe reaction mixture was stirred at RT for 3 h
  4. extractionthe solution was extracted with EtOAc
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated
  8. custompurified by silica gel chromatography (0-30% EtOAc/hexanes)

Sources & evidence

ORD record
ord-73620ff5ede249ffaffdcb6c45f97147
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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