Water → HCID 86698026, compound

HRID 518872Notes

Reaction equation

HRID 518872 reaction equation
IC.[N+:3]([C:6]1[CH:11]=[CH:10][C:9]([N:12]2[CH2:17][CH2:16][CH2:15][C@@H:14]([NH:18][CH:19]3[CH2:22][O:21][CH2:20]3)[CH2:13]2)=[CH:8][C:7]=1[O:23][CH:24]([CH3:26])[CH3:25])([O-:5])=[O:4].[C:27](=O)([O-])[O-].[Cs+].[Cs+].O>CN(C=O)C>[CH3:27][N:18]([CH:19]1[CH2:22][O:21][CH2:20]1)[C@@H:14]1[CH2:15][CH2:16][CH2:17][N:12]([C:9]2[CH:10]=[CH:11][C:6]([N+:3]([O-:5])=[O:4])=[C:7]([O:23][CH:24]([CH3:26])[CH3:25])[CH:8]=2)[CH2:13]1

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodide2×HCID 10796Cesium carbonateHCID 86698025HCID 86698025, compound

Product 1

HCID 86698026HCID 86698026, compoundYield 15.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

65 μl of iodomethane are added, at a temperature of about 20° C., under an argon atmosphere and with magnetic stirring, to a mixture of 293 mg of (3R)-1-[4-nitro-3-(propan-2-yloxy)phenyl]-N-(oxetan-3-yl)piperidin-3-amine and 427 mg of caesium carbonate in 8 ml of anhydrous DMF. After stirring for 3 hours, 100 μl of iodomethane are added and the mixture is left to stir for a further 2 h. 10 ml of water are then added and the mixture is then extracted three times with 15 ml of ethyl acetate. The combined organic phases are dried over magnesium sulfate, filtered and concentrated under vacuum so as to give an oily yellow residue. The residue is purified by flash chromatography on silica gel, using a dichloromethane/methanol (98/2) eluent, so as to obtain 47 mg of (3R)—N-methyl-1-[4-nitro-3-(propan-2-yloxy)phenyl]-N-(oxetan-3-yl)piperidin-3-amine in the form of an orangey-yellow solid.

Workup

  1. waitthe mixture is left
  2. stirringto stir for a further 2 h
  3. extractionthe mixture is then extracted three times with 15 ml of ethyl acetate
  4. dry with materialThe combined organic phases are dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum so as
  7. customto give an oily yellow residue
  8. customThe residue is purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-4271dc22967c4e2699c56adeda41fd61
Source dataset
uspto-grants-2015_08
Patent number
US09115140B2

Reaction notes

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