N-Methoxy-N-methyl-3-(trifluoromethyl)benzamide → [4-(4-Benzyl-morpholin-2-yl)-phenyl]-(3-trifluoromethyl-phenyl)-methanone

HRID 588233Notes

Reaction equation

HRID 588233 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][O:11][CH:10]([C:14]2[CH:19]=[CH:18][C:17](Br)=[CH:16][CH:15]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.CON(C)[C:29](=[O:40])[C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([F:39])([F:38])[F:37])[CH:31]=1>C1COCC1>[CH2:1]([N:8]1[CH2:13][CH2:12][O:11][CH:10]([C:14]2[CH:19]=[CH:18][C:17]([C:29]([C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([F:37])([F:38])[F:39])[CH:31]=3)=[O:40])=[CH:16][CH:15]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 14069349N-Methoxy-N-methyl-3-(trifluoromethyl)benzamideHCID 580978794-Benzyl-2-(4-bromo-phenyl)-morpholineHCID 178418339Butyllithium

Product 1

HCID 66653802[4-(4-Benzyl-morpholin-2-yl)-phenyl]-(3-trifluoromethyl-phenyl)-methanoneYield 34.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 4-benzyl-2-(4-bromo-phenyl)-morpholine (1.89 g, 5.7 mmol) in THF (30 mL), at −78° C., was added dropwise n-butyl lithium (2.85 mL; 2.5 mol/l in hexanes; 7.1 mmol). The mixture was stirred for 20 min. at −78° C., and subsequently N-Methoxy-N-methyl-3-trifluoromethyl-benzamide (2.66 g, 11.4 mmol) was added. The mixture was allowed to warm to RT and stirred overnight. The resulting mixture was partitioned between an aqueous saturated NH4Cl solution and EtOAc. The layers were separated. The organic layer was washed with a saturated aqueous NaHCO3-solution, dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (EtOAc:heptanes 1:3) to afford [4-(4-benzyl-morpholin-2-yl)-phenyl]-(3-trifluoromethyl-phenyl)-methanone (0.84 g), which was used as such in the next step.

Workup

  1. temperatureto warm to RT
  2. stirringstirred overnight
  3. customThe resulting mixture was partitioned between an aqueous saturated NH4Cl solution and EtOAc
  4. customThe layers were separated
  5. washThe organic layer was washed with a saturated aqueous NaHCO3-solution
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by column chromatography (EtOAc:heptanes 1:3)

Sources & evidence

ORD record
ord-95d3ef5b00f24553921bd341443f187d
Source dataset
uspto-grants-2016_01
Patent number
US09227960B2

Reaction notes

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