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

HRID 571780노트

반응식

HRID 571780 반응식
[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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
-78 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-524c2a0f7b4c41079c120d05098835de
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09029371B2

반응 노트

불러오는 중…