Dimethyl Sulfoxide → 1,1-dimethylethyl (2S)-2-(1-methylethyl)-4-[3-(methyloxy)-4-nitrophenyl]-1-piperazinecarboxylate

HRID 419672Notes

Reaction equation

HRID 419672 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7](F)[CH:6]=[CH:5][C:4]=1[N+:10]([O-:12])=[O:11].C([O-])([O-])=O.[K+].[K+].CS(C)=O.[CH3:23][CH:24]([C@H:26]1[CH2:31][NH:30][CH2:29][CH2:28][N:27]1[C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH3:25]>C1COCC1.CCOC(C)=O.O>[CH3:25][CH:24]([C@H:26]1[CH2:31][N:30]([C:7]2[CH:6]=[CH:5][C:4]([N+:10]([O-:12])=[O:11])=[C:3]([O:2][CH3:1])[CH:8]=2)[CH2:29][CH2:28][N:27]1[C:32]([O:34][C:35]([CH3:37])([CH3:36])[CH3:38])=[O:33])[CH3:23]

Participants

8

Reactant 4

HCID 679Dimethyl SulfoxideHCID 11430Potassium CarbonateHCID 27792505-Fluoro-2-nitroanisoleHCID 17750439(2S)-2-Isopropylpiperazine, N1-BOC protected

Product 1

HCID 594527611,1-dimethylethyl (2S)-2-(1-methylethyl)-4-[3-(methyloxy)-4-nitrophenyl]-1-piperazinecarboxylateYield 60%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-Fluoro-2-(methyloxy)-1-nitrobenzene (Example 22, step A) (0.429 g, 2.51 mmol), and K2CO3 (0.410 g, 2.97 mmol) were placed in a flask with 14 mL of DMSO and stirred with a stir bar. 1,1-Dimethylethyl (2S)-2-(1-methylethyl)-1-piperazinecarboxylate (0.521 g, 2.28 mmol) was dissolved in 6.6 mL of THF and added via syringe. The mixture was stirred for 8 days and poured into H2O and EtOAc. The layers were separated, and the organic layer was washed with brine. The combined aqueous layers were extracted with EtOAc. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. Purification by flash chromatography afforded the title compound of step D (0.515 g, 1.36 mmol, 60%). 1H NMR (400 MHz, DMSO-d6) δ 7.84 (d, J=9.3 Hz, 1H), 6.54 (dd, J=9.4, 2.3 Hz, 1H), 6.43 (d, J=2.4 Hz, 1H), 4.01 (d, J=13.5 Hz, 1H), 3.86 (s, 5H), 3.60-3.75 (m, 1H), 3.22-3.28 (m, 1H), 3.06 (dd, J=13.6, 3.7 Hz, 1H), 2.90-3.02 (m, 1H), 1.79-1.92 (m, 1H), 1.37 (s, 9H), 0.92 (d, J=6.6 Hz, 3H), 0.75 (d, J=6.8 Hz, 3H).

Workup

  1. additionadded via syringe
  2. stirringThe mixture was stirred for 8 days
  3. customThe layers were separated
  4. washthe organic layer was washed with brine
  5. extractionThe combined aqueous layers were extracted with EtOAc
  6. dry with materialThe combined organic layers were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification by flash chromatography

Sources & evidence

ORD record
ord-8b16f43845064ad99b187f1f5c0d007f
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

Loading…