Potassium Carbonate → Tert-butyl 3-(4-nitrophenyl)-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylate

HRID 1520039Notes

Reaction equation

HRID 1520039 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:19]2[CH2:25][CH:24]3[N:26]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH:21]([CH2:22][CH2:23]3)[CH:20]=2)O1.C(=O)([O-])[O-].[K+].[K+]>C1OCCOC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[N+:8]([C:5]1[CH:6]=[CH:7][C:2]([C:19]2[CH2:20][CH:21]3[N:26]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH:24]([CH2:23][CH2:22]3)[CH:25]=2)=[CH:3][CH:4]=1)([O-:10])=[O:9]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 114661-Bromo-4-nitrobenzeneHCID 53393373Tert-butyl 3-(tetramethyl-1,3,2-dioxaborolan-2-yl)-8-azabicyclo(3.2.1)oct-2-ene-8-carboxylate

Product 1

HCID 67981656Tert-butyl 3-(4-nitrophenyl)-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylateYield 60.2%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 1-bromo-4-nitrobenzene (2.0 g; 9.9 mmol; 1.0 eq.), tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylate (4.3 g; 12.9 mmol; 1.30 eq.), PdCl2(dppf) (724 mg; 0.99 mmol; 0.1 eq.) and potassium carbonate (4.1 g; 29.7 mmol; 3.0 eq.) in Dioxane-1,4 (20 mL) and water (10 mL) was heated at 900 under nitrogen atmosphere O/N. The reaction mixture was filtered through a celite pad. The cake was rinsed with dichloromethane, phases were separated and organic phase was washed with water and brine. Organic phase was then dried over magnesium sulfate, filtered and concentrated. The crude was purified by flash chromatography on silica (heptane/EtOAc, gradient from 90:10 to 80:20) to give the title compound as a yellow solid (1.97 g; 60%). 1H NMR (300 MHz, DMSO-d6-d6) δ: 8.17 (d, J=9.0 Hz, 2H), 7.69 (d, J=9.0 Hz, 2H), 6.84 (d, J=5.3 Hz, 1H), 4.43 (t, J=5.3 Hz, 1H), 4.35 (m, 1H), 2.97 (d, J=17.5 Hz, 1H), 2.32 (d, J=17.5 Hz, 1H), 2.15 (m, 1H), 1.95-1.88 (m, 2H), 1.71-1.58 (m, 1H), 1.37 (s, 9H). HPLC (max plot) 89.0%; Rt %4.66 min. UPLC/MS: (MS+) 331.3.

Workup

  1. temperaturewas heated at 900 under nitrogen atmosphere O/N
  2. filtrationThe reaction mixture was filtered through a celite pad
  3. washThe cake was rinsed with dichloromethane, phases
  4. customwere separated
  5. washorganic phase was washed with water and brine
  6. dry with materialOrganic phase was then dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude was purified by flash chromatography on silica (heptane/EtOAc, gradient from 90:10 to 80:20)

Sources & evidence

ORD record
ord-5005c552d32c4ef693a588c41f9bc5d3
Source dataset
uspto-grants-2015_07
Patent number
US09073892B2

Reaction notes

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