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

HRID 1850737Notes

Reaction equation

HRID 1850737 reaction equation
[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]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 61436Stannous chloride dihydrateHCID 867111861-(3-isopropyl-1,2,4-oxadiazol-5-yl)-4-{(1R,2S)-2-[2-(4-nitrophenoxy)ethyl]cyclopropyl}piperidine

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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]+.

Workup

  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

Sources & evidence

ORD record
ord-8452e854d8864bbb87d7a90f13f155d6
Source dataset
uspto-grants-2015_02
Patent number
US08957062B2

Reaction notes

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