Cesium carbonate → Tert-butyl 8-(6-nitropyridin-3-yl)-3,8-diazabicyclo[3.2.1]octane-3-carboxylate

HRID 1411626Notes

Reaction equation

HRID 1411626 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([N+:8]([O-:10])=[O:9])=[N:6][CH:7]=1.[CH:11]12[NH:18][CH:15]([CH2:16][CH2:17]1)[CH2:14][N:13]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:12]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].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.O1CCOCC1>[N+:8]([C:5]1[N:6]=[CH:7][C:2]([N:18]2[CH:11]3[CH2:17][CH2:16][CH:15]2[CH2:14][N:13]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:12]3)=[CH:3][CH:4]=1)([O-:10])=[O:9]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 8176205-Bromo-2-nitropyridineHCID 21904757tert-Butyl 3,8-diazabicyclo[3.2.1]octane-3-carboxylate

Product 1

HCID 66743231Tert-butyl 8-(6-nitropyridin-3-yl)-3,8-diazabicyclo[3.2.1]octane-3-carboxylateYield 191.8%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A 250-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 1,4-dioxane (100 mL), 5-bromo-2-nitropyridine (2.5 g, 12.4 mmol), tert-butyl 3,8-diazabicyclo[3.2.1]octane-3-carboxylate (869 g, 4.1 mmol), Pd2(dba)3 (193 mg, 0.21 mmol), XantPhos (237 mg, 0.41 mmol), and cesium carbonate (2.7 g, 8.2 mmol). After three cycles of vacuum/argon flush, the mixture was stirred at 110° C. overnight. The reaction was cooled to room temperature. It was then filtered and the filtrate was evaporated in vacuo. The residue was purified by silica-gel column chromatography eluting with 3:1 petroleum ether/ethyl acetate to afford 152a (2.63 g, 66.8%) as a yellow solid. MS-ESI: [M+H]+ 335.2.

Workup

  1. customA 250-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter three cycles of vacuum/argon flush
  3. temperatureThe reaction was cooled to room temperature
  4. filtrationIt was then filtered
  5. customthe filtrate was evaporated in vacuo
  6. customThe residue was purified by silica-gel column chromatography
  7. washeluting with 3:1 petroleum ether/ethyl acetate

Sources & evidence

ORD record
ord-8b9f178ba7c943b1b0a94ee3dcf4fd30
Source dataset
uspto-grants-2014_12
Patent number
US08921353B2

Reaction notes

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