Cesium carbonate → Tert-butyl 4-(3-methoxy-4-nitrophenyl)piperazine-1-carboxylate

HRID 1014203Notes

Reaction equation

HRID 1014203 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[C:4]([O:11][CH3:12])[CH:3]=1.[N:13]1([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:12][O:11][C:4]1[CH:3]=[C:2]([N:16]2[CH2:15][CH2:14][N:13]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:18][CH2:17]2)[CH:7]=[CH:6][C:5]=1[N+:8]([O-:10])=[O:9]

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 811105-Chloro-2-nitroanisoleHCID 143452tert-Butyl piperazine-1-carboxylateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)

Product 1

HCID 25918710Tert-butyl 4-(3-methoxy-4-nitrophenyl)piperazine-1-carboxylateYield 73.7%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
100 °C

Procedure

4-chloro-2-(methyloxy)-1-nitrobenzene (10 g, 53.2 mmol, Aldrich), 1,1-dimethylethyl 1-piperazinecarboxylate (20 g, 107.5 mmol), cesium carbonate (35.0 g, 107.5 mmol), Pd2dba3 (5 g, 5.5 mmol), and XANTPHOS (4.62 g, 8.0 mmol) were added to degassed dioxane (100 mL) and heated to 100° C. under a water cooled reflux condenser for 12 hours. The dioxane was removed under reduced pressure and the solids were partitioned between methylene chloride (500 mL) and water (500 mL). The organic layer was dried over sodium sulfate, taken to a residue under reduced pressure, and triturated with a methylene choride/hexanes mixture (15:85) to precipitate out analytically pure 1-dimethylethyl 4-[3-(methyloxy)-4-nitrophenyl]-1-piperazinecarboxylate as a yellow solid (13.2 g, 39.2 mmol, 73% yield). 1H NMR (400 MHz, CDCl3) δ ppm 1.49 (s, 9 H), 3.33-3.42 (m, 4 H), 3.62-3.64 (m, 4 H), 3.96 (s, 3 H), 6.39 (s, 1 H), 6.44 (dd, J=9.16, 2.56 Hz, 1 H), 8.01 (d, J=9.16 Hz, 1 H).

Workup

  1. customto degassed dioxane (100 mL)
  2. temperaturecooled
  3. temperaturereflux condenser for 12 hours
  4. customThe dioxane was removed under reduced pressure
  5. customthe solids were partitioned between methylene chloride (500 mL) and water (500 mL)
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. customtriturated with a methylene choride/hexanes mixture (15:85)

Sources & evidence

ORD record
ord-67673d6886b846e5973eeabc4e3704bc
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

Loading…