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

HRID 1520039ノート

反応式

HRID 1520039 の反応式
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]

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-5005c552d32c4ef693a588c41f9bc5d3
出典データセット
uspto-grants-2015_07
特許番号
US09073892B2

反応ノート

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