Dimethyl Sulfoxide → 4-(3,5-Difluoro-2-nitro-phenyl)-morpholine

HRID 1687657Notes

Reaction equation

HRID 1687657 reaction equation
F[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[C:4]([F:9])[C:3]=1[N+:10]([O-:12])=[O:11].C([O-])([O-])=O.[K+].[K+].CS(C)=O.[NH:23]1[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>CCOC(C)=O>[F:9][C:4]1[C:3]([N+:10]([O-:12])=[O:11])=[C:2]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[CH:7]=[C:6]([F:8])[CH:5]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8083MorpholineHCID 11430Potassium CarbonateHCID 675671,3,5-Trifluoro-2-nitrobenzene

Product 1

HCID 672635064-(3,5-Difluoro-2-nitro-phenyl)-morpholine

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

1,3,5-Trifluoro-2-nitro-benzene (5.30 g, 29.9 mmol) and K2CO3 (4.96 g, 35.9 mmol) were mixed in DMSO (40.0 mL, 564 mmol) and morpholine (2.74 mL, 31.4 mmol) was added. The reaction was stirred at rt for 48 h, diluted with EtOAc and washed twice with water. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. Title compound isolated as a yellow oil (4.26 g, 58%). LCMS (m/e) 245 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 6.67-6.58 (m, 2H), 3.80 (t, 4H, J=4.2 Hz), 3.06 (t, 4H, J=4.2 Hz), 19F-NMR (CDCl3, 400 MHz) δ −102, −118. Also obtained in this reaction, 4-(3,5-difluoro-4-nitro-phenyl)-morpholine as a yellow solid (2.85 g, 39%). m.p.=112-114° C.; LCMS (m/e) 245 (M+H); 1H-NMR (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); 19F-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

Sources & evidence

ORD record
ord-8423e88edc8f4824aae5ea0b39f5f815
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

Loading…