Morpholine → 4-(2,5-Difluoro-4-nitrophenyl)morpholine

HRID 1407226Notes

Reaction equation

HRID 1407226 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[C:5]([F:11])=[CH:4][C:3]=1F.[NH:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1.C([O-])([O-])=O.[K+].[K+]>CS(C)=O.CCOC(C)=O>[F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[C:5]([F:11])=[CH:4][C:3]=1[N:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1

Participants

6

Reactant 3

HCID 8083MorpholineHCID 11430Potassium CarbonateHCID 750121,2,4-Trifluoro-5-nitrobenzene

Product 1

HCID 580722644-(2,5-Difluoro-4-nitrophenyl)morpholineYield 117%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 1,2,4-trifluoro-5-nitrobenzene (4.0 mL, 35 mmol), morpholine (3.1 mL, 35 mmol), and K2CO3 (4.8 g, 35 mmol) in DMSO (35 mL) was stirred at room temperature overnight. The mixture was diluted with AcOEt and washed with water and brine. The organic layer was dried over MgSO4, and concentrated under reduced pressure. The residue was recrystallized from AcOEt to give the title compound (10 g, 63% yield) as a pale yellow solid: NMR (300 MHz, DMSO-d6): δ ppm 3.15-3.49 (4H, m), 3.50-3.90 (4H, m), 7.13 (1H, dd, J=14.3, 7.5 Hz), 8.01 (1H, dd, J=13.6, 7.5 Hz). LC-MS (ESI) m/z 245 [M+H]+.

Workup

  1. washwashed with water and brine
  2. dry with materialThe organic layer was dried over MgSO4
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was recrystallized from AcOEt

Sources & evidence

ORD record
ord-71bec1e4e32c4e33941d6c945400224c
Source dataset
uspto-grants-2014_12
Patent number
US08916566B2

Reaction notes

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