Hydrochloric Acid → (4-Benzyloxy-3-methoxy-phenyl)-(2-trifluoromethyl-pyridin-3-yl)-methanone

HRID 1920066Notes

Reaction equation

HRID 1920066 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12](Br)=[CH:11][C:10]=1[O:16][CH3:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.CON(C)[C:26](=[O:37])[C:27]1[CH:32]=[CH:31][CH:30]=[N:29][C:28]=1[C:33]([F:36])([F:35])[F:34].Cl>O1CCCC1>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:26]([C:27]2[C:28]([C:33]([F:36])([F:34])[F:35])=[N:29][CH:30]=[CH:31][CH:32]=2)=[O:37])=[CH:11][C:10]=1[O:16][CH3:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 36131281-(Benzyloxy)-4-bromo-2-methoxybenzeneHCID 71445792N-Methoxy-N-methyl-2-(trifluoromethyl)nicotinamideHCID 178418339Butyllithium

Product 1

HCID 67037150(4-Benzyloxy-3-methoxy-phenyl)-(2-trifluoromethyl-pyridin-3-yl)-methanone

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 4-benzyloxy-3-methoxy-bromobenzene (2.0 g, 6.82 mmol) in tetrahydrofuran (50 mL) at −78° C. under argon was added 2 N butyllithium solution in hexanes (3.75 mL, 7.5 mmol) dropwise. The resulting mixture was allowed to stir for one hour, whereupon a solution of N-methoxy-N-methyl-2-trifluoromethyl-nicotinamide (1.76 g, 7.5 mmol) in tetrahydrofuran (20 mL) was added dropwise. The mixture was then allowed to reach room temperature over two hours, then poured onto cold 2 N aqueous hydrochloric acid (150 mL). The mixture was extracted with diethylether, and the combined organic layers were washed with water and brine, dried over anhydrous sodium sulphate and filtered. Evaporation of the solvent left a brown oil that was chromatographed over silica gel (petroleum ether/ethyl acetate, 2:1) to give (4-benzyloxy-3-methoxy-phenyl)-(2-trifluoromethyl-pyridin-3-yl)-methanone, 1.72 g (65%).

Workup

  1. additionwas added dropwise
  2. extractionThe mixture was extracted with diethylether
  3. washthe combined organic layers were washed with water and brine
  4. dry with materialdried over anhydrous sodium sulphate
  5. filtrationfiltered
  6. customEvaporation of the solvent
  7. waitleft a brown oil that
  8. customwas chromatographed over silica gel (petroleum ether/ethyl acetate, 2:1)

Sources & evidence

ORD record
ord-5fef0350eb4d4e64a8e90892b8cd21ce
Source dataset
uspto-grants-2012_05
Patent number
US08168793B2

Reaction notes

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