Cesium carbonate → 1-{3-[5-Bromo-2-(5-trifluoromethyl-furan-2-ylmethoxy)-benzyl]-azetidin-1-yl}-2,2,2-trifluoro-ethanone

HRID 237302노트

반응식

HRID 237302 반응식
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([OH:19])=[C:6]([CH:18]=1)[CH2:7][CH:8]1[CH2:11][N:10]([C:12](=[O:17])[C:13]([F:16])([F:15])[F:14])[CH2:9]1.C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:27][C:28]1[O:29][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:31][CH:32]=1.C(=O)(O)[O-].[Na+]>CN(C=O)C.CCOC(C)=O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:19][CH2:27][C:28]2[O:29][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:31][CH:32]=2)=[C:6]([CH:18]=1)[CH2:7][CH:8]1[CH2:11][N:10]([C:12](=[O:17])[C:13]([F:15])([F:16])[F:14])[CH2:9]1

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 516892Sodium BicarbonateHCID 27946052-(Bromomethyl)-5-(trifluoromethyl)furanHCID 584051121-[3-(5-Bromo-2-hydroxy-benzyl)-azetidin-1-yl]-2,2,2-trifluoro-ethanone

생성물 1

HCID 866570631-{3-[5-Bromo-2-(5-trifluoromethyl-furan-2-ylmethoxy)-benzyl]-azetidin-1-yl}-2,2,2-trifluoro-ethanone수율 91.9%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 1-[3-(5-bromo-2-hydroxy-benzyl)-azetidin-1-yl]-2,2,2-trifluoro-ethanone (59 mg, 0.17 mmol) in DMF (10 mL) was added KI (40 mg, 0.24 mmol), Cs2CO3 (170 mg, 0.51 mmol) and 2-bromomethyl-5-trifluoromethyl-furan (56 mg, 0.24 mmol). After 16 h, saturated sodium bicarbonate solution and EtOAc were added. The aqueous portion was extracted three times with EtOAc and the combined organic were dried (Na2SO4) and concentrated. The crude product was purified by RP HPLC (basic conditions) to provide the title compound (76 mg, 91%). MS (ESI): mass calcd. for C18H14BrF6NO3, 486.2; m/z found, 488.1 [M+H]+. 1H NMR (CDCl3): 7.34 (dd, J=8.7, 2.5 Hz, 1H), 7.21 (d, J=2.5 Hz, 1H), 6.89-6.76 (m, 2H), 6.48 (d, J=3.4 Hz, 1H), 5.02 (s, 2H), 4.40 (dd, J=9.6, 8.4 Hz, 1H), 4.22-4.11 (m, 1H), 4.08-4.02 (m, 1H), 3.84 (dd, J=10.7, 5.7 Hz, 1H), 3.11-2.97 (m, 1H), 2.97-2.82 (m, 2H).

후처리

  1. extractionThe aqueous portion was extracted three times with EtOAc
  2. dry with materialthe combined organic were dried (Na2SO4)
  3. concentrationconcentrated
  4. customThe crude product was purified by RP HPLC (basic conditions)

출처 및 근거

ORD 기록
ord-ed2f275d40e14e7789927e4cf81f462d
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08642583B2

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