Potassium Carbonate → HCID 86636431, compound

HRID 1471531Notes

Reaction equation

HRID 1471531 reaction equation
Cl[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([O:10][CH2:11][CH2:12][O:13][CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][O:15]2)[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]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([O:10][CH2:11][CH2:12][O:13][CH:14]3[CH2:19][CH2:18][CH2:17][CH2:16][O:15]3)[N:3]=2)=[CH:25][C:22]=1[CH:23]=[O:24]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 3871792-Bromo-5-hydroxybenzaldehydeHCID 86636432HCID 86636432, compound

Product 1

HCID 86636431HCID 86636431, compoundYield 71.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 6-chloro-2-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-nicotinonitrile (2.4 g, 8.48 mmol) and 2-bromo-5-hydroxy-benzaldehyde (1.87 g, 9.33 mmol) in DMF (25 mL) was added potassium carbonate (1.75 g, 12.69 mmol). The resulting mixture was heated at 80° C. overnight. DMF was removed under reduced pressure, the residue was diluted with EtOAc (200 mL), 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 5-25% EtOAc/hexanes as gradient elution yielding the title compound (2.7 g, 71%) as white solid. 1H NMR (400 MHz, CDCl3) δ ppm 10.35 (s, 1 H), 7.88 (d, J=8.2 Hz, 1 H), 7.75 (d, J=2.7 Hz, 1 H), 7.70 (d, J=8.2 Hz, 1 H), 7.28 (dd, J=8.6, 3.5 Hz, 1 H), 6.60 (d, J=8.2 Hz, 1 H), 4.64 (s, 1 H), 4.28 (t, J=4.9 Hz, 2 H), 3.97-3.80 (m, 2 H), 3.72-3.60 (m, 1 H), 3.55-3.42 (m, 1 H), 1.84-1.64 (m, 2 H), 1.61-1.49 (m, 4 H).

Workup

  1. customDMF was removed under reduced pressure
  2. additionthe residue was diluted with EtOAc (200 mL)
  3. washwashed 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 5-25% EtOAc/hexanes as gradient elution

Sources & evidence

ORD record
ord-76c8adb49a5941788655c1fbd3db35a8
Source dataset
uspto-grants-2015_04
Patent number
US09012431B2

Reaction notes

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