Cesium carbonate → Tert-butyl 4-(4-(1,3-dioxoisoindolin-2-yl)-3-nitrophenyl)piperazine-1-carboxylate

HRID 58200Notes

Reaction equation

HRID 58200 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16](=[O:17])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]2=[O:18])=[C:4]([N+:19]([O-:21])=[O:20])[CH:3]=1.[N:22]1([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1.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.C([O-])([O-])=O.[Cs+].[Cs+]>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]>[O:18]=[C:9]1[C:10]2[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:16](=[O:17])[N:8]1[C:5]1[CH:6]=[CH:7][C:2]([N:25]2[CH2:24][CH2:23][N:22]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:27][CH2:26]2)=[CH:3][C:4]=1[N+:19]([O-:21])=[O:20]

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 143452tert-Butyl piperazine-1-carboxylateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 1180254582-(4-Bromo-2-nitrophenyl)isoindoline-1,3-dione

Product 1

HCID 118025495Tert-butyl 4-(4-(1,3-dioxoisoindolin-2-yl)-3-nitrophenyl)piperazine-1-carboxylateYield 43.4%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
100 °C

Procedure

2-(4-bromo-2-nitrophenyl)isoindoline-1,3-dione (500 g, 1.4 mmol), tert-butyl piperazine-1-carboxylate (402 g, 2.2 mmol), Pd2(dba)3 (66.0 g, 0.07 mmol), Xantphos (83 g, 0.144 mmol) and Cs2CO3 (939 g, 2.9 mmol) were placed in reaction vial (microwave reaction vial 10-20 ml) and purged with nitrogen. Toluene (5.0 ml) was added and nitrogen was bubbled for 10 min. The reaction mixture was heated at 100° C. for 5 hours. Heating was stopped and cooled to rt. The reaction mixture was filtered through a pad of celite and filtrate was evaporated. The remaining material was purified by flash chromatography on silica eluting with 20% to 70% EtOAc/Hexane to afford the title compound (275 mg, yield: 42%). 1H-NMR (400 MHz, CDCl3) δ 1.51 (s, 6H) 3.28-3.39 (m, 2H) 3.57-3.70 (m, 2H) 7.20-7.24 (m, 1H) 7.35 (d, 1H) 7.66 (d, 1H) 7.75-7.87 (m, 1H) 7.96 (dd, 1H)

Workup

  1. custompurged with nitrogen
  2. additionToluene (5.0 ml) was added
  3. customnitrogen was bubbled for 10 min
  4. temperatureHeating
  5. temperaturecooled to rt
  6. filtrationThe reaction mixture was filtered through a pad of celite and filtrate
  7. customwas evaporated
  8. customThe remaining material was purified by flash chromatography on silica eluting with 20% to 70% EtOAc/Hexane

Sources & evidence

ORD record
ord-78c4e108dd2442049c621126984a1361
Source dataset
uspto-grants-2016_09
Patent number
US09434697B2

Reaction notes

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