乙酸乙酯 → 4-(2-{(1S,2R)-2-[1-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-4-yl]cyclopropyl}ethoxy)aniline

HRID 1850737笔记

反应方程式

HRID 1850737 反应方程式
[CH:1]([C:4]1[N:8]=[C:7]([N:9]2[CH2:14][CH2:13][CH:12]([C@H:15]3[CH2:17][C@H:16]3[CH2:18][CH2:19][O:20][C:21]3[CH:26]=[CH:25][C:24]([N+:27]([O-])=O)=[CH:23][CH:22]=3)[CH2:11][CH2:10]2)[O:6][N:5]=1)([CH3:3])[CH3:2].O.O.[Sn](Cl)Cl.C(OCC)(=O)C>CN(C=O)C>[CH:1]([C:4]1[N:8]=[C:7]([N:9]2[CH2:14][CH2:13][CH:12]([C@H:15]3[CH2:17][C@H:16]3[CH2:18][CH2:19][O:20][C:21]3[CH:26]=[CH:25][C:24]([NH2:27])=[CH:23][CH:22]=3)[CH2:11][CH2:10]2)[O:6][N:5]=1)([CH3:3])[CH3:2]

参与物

5

反应物 3

HCID 8857乙酸乙酯HCID 61436氯化亚锡二水合物HCID 867111861-(3-isopropyl-1,2,4-oxadiazol-5-yl)-4-{(1R,2S)-2-[2-(4-nitrophenoxy)ethyl]cyclopropyl}piperidine

产物 1

HCID 867111874-(2-{(1S,2R)-2-[1-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-4-yl]cyclopropyl}ethoxy)aniline

试剂、催化剂与溶剂 1

HCID 6228N,N-二甲基甲酰胺溶剂

实验过程

To a solution of 1-(3-isopropyl-1,2,4-oxadiazol-5-yl)-4-{(1R,2S)-2-[2-(4-nitrophenoxy)ethyl]cyclopropyl}piperidine (353 mg, 0.881 mmol) in DMF (5 ml) was added at tin(II) chloride dihydrate (994 mg, 4.41 mmol) and the resulting mixture stirred at room temperature for 2 hours, then heated to 50° C. for 13 hours. Ethyl acetate (50 mL) was added and the solution washed with saturated aqueous sodium hydrogen carbonate followed by brine. The organic layer was dried over sodium sulfate, filtered, and the solvent was evaporated under reduced pressure (328 mg). The residue was purified by flash chromatography on silica gel using a 25 g column, eluting with 1 column volume of DCM, followed by a linear gradient of ethyl acetate in DCM from 0% to 100% over 15 column volumes, to afford the title compound. LCMS: retention 0.79 min/2.0 minute run: (ESI) m/z 371 [M+H]+.

后处理

  1. temperatureheated to 50° C. for 13 hours
  2. washthe solution washed with saturated aqueous sodium hydrogen carbonate
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. customthe solvent was evaporated under reduced pressure (328 mg)
  6. customThe residue was purified by flash chromatography on silica gel using a 25 g column
  7. washeluting with 1 column volume of DCM

来源与证据

ORD记录
ord-8452e854d8864bbb87d7a90f13f155d6
来源数据集
uspto-grants-2015_02
专利号
US08957062B2

反应笔记

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