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

HRID 237302ノート

反応式

HRID 237302 の反応式
[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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-ed2f275d40e14e7789927e4cf81f462d
出典データセット
uspto-grants-2014_02
特許番号
US08642583B2

反応ノート

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