Cesium carbonate → 1,1-Dimethylethyl (6-formyl-3-pyridinyl)methylcarbamate

HRID 906377Notes

Reaction equation

HRID 906377 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([CH:8]=[O:9])=[N:6][CH:7]=1.[CH3:10][NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15].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.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[CH:8]([C:5]1[N:6]=[CH:7][C:2]([CH2:10][NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:3][CH:4]=1)=[O:9]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 527635tert-Butyl methylcarbamateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 98775625-Bromopyridine-2-carbaldehyde

Product 1

HCID 866181111,1-Dimethylethyl (6-formyl-3-pyridinyl)methylcarbamateYield 51.3%

Reagents, catalysts & solvents 2

HCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 5-bromo-2-pyridinecarbaldehyde (1.5 g, 8.064 mmol), 1,1-dimethylethyl methylcarbamate (D58) (1.267 g, 9.677 mmol), tris(dibenzylideneacetone) dipalladium(0) (0.148 g, 0.161 mmol), xantphos (0.373 g, 0.645 mmol) and cesium carbonate (3.678 g, 11.289 mmol) in dioxane (35 mL) was heated at 110° C. overnight under an argon atmosphere. On cooling, the solvent was removed in vacuo and the residue partitioned between EtOAc and water. The organic layer was separated, washed with water and brine, dried and concentrated to give the crude product which was purified by column chromatography. Elution with 0-50% ether/petroleum ether gave the title compound as a brown oil (0.977 g). δH (CDCl3, 400 MHz) 10.01 (1H, s), 8.79 (1H, d), 7.94 (1H, d), 7.86 (1H, dd), 3.40 (3H, s), 1.53 (9H, s). MS (ES): 259.1 (MNa+), 181.2, no molecular ion (MH+) observed.

Workup

  1. temperatureOn cooling
  2. customthe solvent was removed in vacuo
  3. customthe residue partitioned between EtOAc and water
  4. customThe organic layer was separated
  5. washwashed with water and brine
  6. customdried
  7. concentrationconcentrated
  8. customto give the crude product which
  9. customwas purified by column chromatography
  10. washElution with 0-50% ether/petroleum ether

Sources & evidence

ORD record
ord-d0dd5d2d61794ca6bac2941f2fffab26
Source dataset
uspto-grants-2011_09
Patent number
US08012981B2

Reaction notes

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