Sodium Iodide → 4-(5-Bromo-2-fluorophenyl)morpholine

HRID 2240998Notes

Reaction equation

HRID 2240998 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:9])=[C:6]([CH:8]=1)[NH2:7].[I-].[Na+].C(=O)([O-])[O-].[K+].[K+].Cl[CH2:19][CH2:20][O:21][CH2:22][CH2:23]Cl>CN(C)C=O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:9])=[C:6]([N:7]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[CH:8]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 8115Bis(2-chloroethyl) etherHCID 11430Potassium CarbonateHCID 27694075-Bromo-2-fluoroaniline

Product 1

HCID 593053644-(5-Bromo-2-fluorophenyl)morpholineYield 29%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a CEM snap top microwave vial (10 ml) equipped with a magnetic stir bar (3×10 mm) was added 5-Bromo-2-fluoroaniline (1.00 g, 5.26 mmol), sodium iodide (2.37 gm, 15.8 mmol), potassium carbonate (1.45 gm, 10.5 mmol), and 2-chloroethyl ether (1.30 gm, 9.09 mmol) in dimethylformamide (6.5 mL). The reaction was capped and irradiated in a CEM Explorer microwave at 120° C. for 4 hours then forced air-cooled. Purification by column chromatography [default gradient (ISCO); EtOAc/hexanes] afforded 397 mg (29%) an oil; 1H NMR (400 MHz, DMSO-d6) δ ppm 3.00 (t, J=1.7 Hz, 4H) 3.69-3.73 (m, 4H) 7.10-7.15 (m, 3H); MS (EI) m/z 259.0 [M+·].

Workup

  1. customTo a CEM snap top microwave vial (10 ml) equipped with a magnetic stir bar (3×10 mm)
  2. customThe reaction was capped
  3. customirradiated in a CEM Explorer microwave at 120° C. for 4 hours
  4. temperaturethen forced air-cooled
  5. customPurification by column chromatography [default gradient (ISCO); EtOAc/hexanes]

Sources & evidence

ORD record
ord-104035ba95574ad0838621a5a7271dbc
Source dataset
uspto-grants-2010_05
Patent number
US07723368B2

Reaction notes

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