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

HRID 1520039노트

반응식

HRID 1520039 반응식
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]

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 312751,4-Dioxane용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-5005c552d32c4ef693a588c41f9bc5d3
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09073892B2

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