Morpholine → 4-(3,5-Difluoro-4-nitro-phenyl)-morpholine

HRID 1041671Notes

Reaction equation

HRID 1041671 reaction equation
[F:1][C:2]1[CH:7]=[C:6](F)[CH:5]=[C:4]([F:9])[C:3]=1[N+:10]([O-:12])=[O:11].C(=O)([O-])[O-].[K+].[K+].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>CS(C)=O.CCOC(C)=O>[F:1][C:2]1[CH:7]=[C:6]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)[CH:5]=[C:4]([F:9])[C:3]=1[N+:10]([O-:12])=[O:11]

Participants

6

Reactant 3

HCID 8083MorpholineHCID 11430Potassium CarbonateHCID 675671,3,5-Trifluoro-2-nitrobenzene

Product 1

HCID 668621544-(3,5-Difluoro-4-nitro-phenyl)-morpholineYield 39%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

1,3,5-Trifluoro-2-nitro-benzene (5.30 g, 0.0299 mol) and Potassium carbonate (4.96 g, 0.0359 mol) were mixed in Dimethyl sulfoxide (40.0 mL) and Morpholine (2.74 mL, 0.0314 mol) was added. The reaction was stirred at room temperature for 48 hours and then diluted with EtOAc and washed twice with water. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification by silica gel chromatography using a gradient of 0-40% EtOAc/hex as the eluting solvent gave 4-(3,5-Difluoro-4-nitro-phenyl)-morpholine (2.85 g, 39%) as a yellow solid. MP=112-114° C.; LCMS=245 (M+H); HNMR (CDCl3, 400 MHz) δ 6.45-6.37 (m, 2H), 3.86 (t, 4H, J=4.5 Hz), 3.33 (t, 4H, J=4.5 Hz); F19 NMR (CDCl3, 400 MHz) δ −115.

Workup

  1. washwashed twice with water
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customPurification by silica gel chromatography

Sources & evidence

ORD record
ord-5457b79da77347438b6c7c94fe85fab7
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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