2,6-Dimethylmorpholine, cis- → 2,6-Dimethyl-4-[1-(4-nitrophenyl)-piperidin-4-yl]-morpholine

HRID 1910782Notes

Reaction equation

HRID 1910782 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][C:13](=O)[CH2:12][CH2:11]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].[CH3:17][C@H:18]1[O:23][C@@H:22]([CH3:24])[CH2:21][NH:20][CH2:19]1.C([BH3-])#N.[Na+]>C(O)(=O)C>[CH3:24][CH:22]1[O:23][CH:18]([CH3:17])[CH2:19][N:20]([CH:13]2[CH2:14][CH2:15][N:10]([C:7]3[CH:8]=[CH:9][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=3)[CH2:11][CH2:12]2)[CH2:21]1

Participants

5

Reactant 3

HCID 6415002,6-Dimethylmorpholine, cis-HCID 38425621-(4-Nitrophenyl)piperidin-4-oneHCID 5003444Sodium cyanoborohydride

Product 1

HCID 671071802,6-Dimethyl-4-[1-(4-nitrophenyl)-piperidin-4-yl]-morpholineYield 87%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To an ice-cooled solution of 1-(4-nitro-phenyl)-piperidin-4-one (400 mg, 1.8 mmol) in acetic acid was added cis-2,6-dimethyl-morpholine (0.32 mL, 2.68 mmol) and sodium cyanoborohydride (220 mg, 3.50 mmol). The mixture was heated at reflux overnight then allowed to cool and concentrated to dryness under reduced pressure. The residue was partitioned between 5% sodium hydroxide solution and ethyl acetate. The organic phase was washed with water, brine, dried and concentrated to afford 2,6-dimethyl-4-[1-(4-nitrophenyl)-piperidin-4-yl]-morpholine (500 mg, 86%) as a yellow solid.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux overnight
  3. temperatureto cool
  4. concentrationconcentrated to dryness under reduced pressure
  5. customThe residue was partitioned between 5% sodium hydroxide solution and ethyl acetate
  6. washThe organic phase was washed with water, brine
  7. customdried
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-49198e06b90f48bb970dda90f286b79a
Source dataset
uspto-grants-2013_12
Patent number
US08604029B2

Reaction notes

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