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

HRID 571780ノート

反応式

HRID 571780 の反応式
[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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-78 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-524c2a0f7b4c41079c120d05098835de
出典データセット
uspto-grants-2015_05
特許番号
US09029371B2

反応ノート

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