Morpholine → 4-(5-Chloro-2-nitrophenyl)morpholine

HRID 646935

Reaction equation

HRID 646935 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[C:4](F)[CH:3]=1.C([O-])([O-])=O.[K+].[K+].[NH:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[C:4]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[CH:3]=1

Participants

5

Reactant 3

HCID 8083MorpholineHCID 11430Potassium CarbonateHCID 696914-Chloro-2-fluoro-1-nitrobenzene

Product 1

HCID 28296114-(5-Chloro-2-nitrophenyl)morpholineYield 84.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a mixture of 4-chloro-2-fluoronitrobenzene (175 mg, 1.00 mmol) and K2CO3 (139 mg, 1.00 mmol) in toluene (2 mL), morpholine (87 μL, 1.0 mmol) was added at 0° C. The resulting mixture was allowed to warm to RT and stirred overnight. The reaction mixture was concentrated and the product was isolated by flash chromatography on silica (20% EtOAc/hexane) to obtain 4-(5-Chloro-2-nitro-phenyl)-morpholine (205 mg, 67%). This compound (243 mg, 1.00 mmol) was dissolved in 1-methylpiperazine (1 mL) and the resulting mixture was heated at 130° C. overnight. The reaction mixture was diluted with water and the product was extracted with DCM (3×10 mL). The DCM layers were combined, dried (Na2SO4) and concentrated to obtain the title compound (177 mg, 58%). 1H-NMR (CDCl3; 400 MHz): δ 8.04 (d, 1H, J=9.4 Hz), 6.46 (dd, 1H, J=9.4, 2.6 Hz), 6.31 (d, 1H, =2.6 Hz), 3.89 (m, 4H), 3.40 (m, 4H), 3.07 (m, 4H), 2.50 (m, 4H), 2.36 (s, 3H).

Workup

  1. additionwas added at 0° C
  2. concentrationThe reaction mixture was concentrated
  3. customthe product was isolated by flash chromatography on silica (20% EtOAc/hexane)

Sources & evidence

ORD record
ord-9836dd1cd98a4c09a69e7112d04cf5c7
Source dataset
uspto-grants-2010_04
Patent number
US07705042B2

Linked notes

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