Cesium carbonate → tert-Butyl (2-bromo-5-formylpyridin-4-yl)carbamate

HRID 468886Notes

Reaction equation

HRID 468886 reaction equation
[Br:1][C:2]1[CH:9]=[C:8](I)[C:5]([CH:6]=[O:7])=[CH:4][N:3]=1.[C:11](=[O:18])([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[NH2:12].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Br:1][C:2]1[CH:9]=[C:8]([NH:12][C:11](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[C:5]([CH:6]=[O:7])=[CH:4][N:3]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 77922tert-Butyl carbamateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 574695636-Bromo-4-iodonicotinaldehyde

Product 1

HCID 86674965tert-Butyl (2-bromo-5-formylpyridin-4-yl)carbamateYield 40%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 6-bromo-4-iodonicotinaldehyde (50 mg, 0.2 mmol), tert-butyl carbamate (28 mg, 0.24 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (18 mg, 0.03 mmol), palladium acetate (5 mg, 0.02 mmol), and cesium carbonate (100 mg, 0.32 mmol) in 1,4-dioxane (1 mL) was heated at 90° C. for 1 hour. The cooled reaction mixture was diluted with ethyl acetate (50 mL) and washed with water (100 mL). The organic layer was separated, dried over sodium sulfate, filtered, and evaporated in vacuo to afford a residue that was purified by flash chromatography (silica, 4 g, ISCO, 0-50% ethyl acetate in heptane) to afford the title compound as a white solid (18 mg, 40%). 1H NMR (400 MHz, CDCl3) δ 10.42 (s, 1H), 9.93 (s, 1H), 8.61 (s, 1H), 8.50 (s, 1H), 1.55 (s, 9H).

Workup

  1. customThe cooled reaction mixture
  2. washwashed with water (100 mL)
  3. customThe organic layer was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customto afford a residue that
  8. customwas purified by flash chromatography (silica, 4 g, ISCO, 0-50% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-ed420e05303c4d6882c64a656cf89978
Source dataset
uspto-grants-2014_01
Patent number
US08623889B2

Reaction notes

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