Potassium Carbonate → HCID 86636448, compound

HRID 1255710Notes

Reaction equation

HRID 1255710 reaction equation
Cl[C:2]1[CH:9]=[C:8]([O:10][CH2:11][CH2:12][O:13][CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][O:15]2)[C:5]([C:6]#[N:7])=[CH:4][N:3]=1.[Br:20][C:21]1[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][C:22]=1[CH:23]=[O:24].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Br:20][C:21]1[CH:28]=[CH:27][C:26]([O:29][C:2]2[CH:9]=[C:8]([O:10][CH2:11][CH2:12][O:13][CH:14]3[CH2:19][CH2:18][CH2:17][CH2:16][O:15]3)[C:5]([C:6]#[N:7])=[CH:4][N:3]=2)=[CH:25][C:22]=1[CH:23]=[O:24]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 3871792-Bromo-5-hydroxybenzaldehydeHCID 866364476-Chloro-4-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-nicotinonitrile

Product 1

HCID 86636448HCID 86636448, compoundYield 64.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 6-chloro-4-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-nicotinonitrile (4.8 g, 16.62 mmol) and 2-bromo-5-hydroxy-benzaldehyde (4.01 g, 19.94 mmol) in DMF (30 mL) was added potassium carbonate (3.44 g, 24.93 mmol). The resulting mixture was heated at 80° C. overnight. DMF was removed under reduced pressure and the residue was diluted with EtOAc (200 mL). The organic layer was washed with water (20 mL) and brine (3×20 mL), dried over Na2SO4, filtered, and concentrated to give white solid. Purification was accomplished by flash chromatography on silica gel using 2-25% EtOAc/hexanes as gradient elution yielding the title compound (4.8 g, 64%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.19 (s, 1H), 8.46 (s, 1H), 7.88 (d, J=8.6 Hz, 1H), 7.60 (d, J=2.7 Hz, 1H), 7.49 (dd, J=8.6, 2.7 Hz, 1H), 7.09 (s, 1H), 4.75-4.67 (m, 1H), 4.49-4.45 (m, 2H), 4.00-3.89 (m, 1H), 3.85-3.74 (m, 2H), 3.49-3.41 (m, 1H), 1.78-1.53 (m, 2H), 1.39-1.53 (m, 4H).

Workup

  1. customDMF was removed under reduced pressure
  2. additionthe residue was diluted with EtOAc (200 mL)
  3. washThe organic layer was washed with water (20 mL) and brine (3×20 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give white solid
  8. customPurification
  9. washwas accomplished by flash chromatography on silica gel using 2-25% EtOAc/hexanes as gradient elution

Sources & evidence

ORD record
ord-4b686fb5fab543c9b2f35033d89d1b26
Source dataset
uspto-grants-2013_06
Patent number
US08461135B2

Reaction notes

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