Sodium Carbonate → (1S,2R)-4'-(2-Hydroxy-1-methyl-4-pyridin-3-ylbutoxy)biphenyl-3,4-dicarbonitrile

HRID 380033Notes

Reaction equation

HRID 380033 reaction equation
[OH:1][C@H:2]([CH2:15][CH2:16][C:17]1[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=1)[C@H:3]([CH3:14])[O:4][C:5]1[CH:10]=[CH:9][C:8](B(O)O)=[CH:7][CH:6]=1.I[C:24]1[CH:29]=[CH:28][C:27]([C:30]#[N:31])=[C:26]([C:32]#[N:33])[CH:25]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:1][C@H:2]([CH2:15][CH2:16][C:17]1[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=1)[C@H:3]([CH3:14])[O:4][C:5]1[CH:10]=[CH:9][C:8]([C:24]2[CH:29]=[CH:28][C:27]([C:30]#[N:31])=[C:26]([C:32]#[N:33])[CH:25]=2)=[CH:7][CH:6]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 41200244-IodophthalonitrileHCID 54413593(1S,2R)-4-(2-hydroxy-1-methyl-4-pyridin-3-ylbutoxy)benzeneboronic acid

Product 1

HCID 20692742(1S,2R)-4'-(2-Hydroxy-1-methyl-4-pyridin-3-ylbutoxy)biphenyl-3,4-dicarbonitrileYield 23.9%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

Prepared according to the method described in Example 12b) from (1S,2R)-4-(2-hydroxy-1-methyl-4-pyridin-3-ylbutoxy)benzeneboronic acid (0.197 g, Example 33), 4-iodo-1,2-dicyanobenzene (0.421 g, Can. J. Chem., 1985, 63, 3057), 2M aqueous sodium carbonate (0.50 ml) and tetrakis(triphenylphosphine)palladium (0) (0.054 g) in ethanol (3 ml). The reaction mixture was heated in a sealed vial at 90° C. for 4 hours. After cooling, the solution was concentrated under reduced pressure and the residue purified by chromatography over silica eluting with ethyl acetate. The residue was further purified by chromatography over silica gel eluting with dichloromethane:2-propanol (19:1). The residue was then further purified by reverse-phase HPLC eluting a gradient of 25-100% acetonitrile in 0.1 w/v aqueous ammonium acetate solution. The HPLC fractions were concentrated under reduced pressure, the residue dissolved in dichloromethane, filtered and concentrated under reduced pressure. The residue was triturated with ether to give the title to compound as a solid (0.060 g).

Workup

  1. customPrepared
  2. temperatureAfter cooling
  3. concentrationthe solution was concentrated under reduced pressure
  4. customthe residue purified by chromatography over silica eluting with ethyl acetate
  5. customThe residue was further purified by chromatography over silica gel eluting with dichloromethane:2-propanol (19:1)
  6. customThe residue was then further purified by reverse-phase HPLC
  7. washeluting a gradient of 25-100% acetonitrile in 0.1 w/v aqueous ammonium acetate solution
  8. concentrationThe HPLC fractions were concentrated under reduced pressure
  9. dissolutionthe residue dissolved in dichloromethane
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was triturated with ether

Sources & evidence

ORD record
ord-7eecc135ef1e4752837b9b4fe30b1de9
Source dataset
uspto-grants-2001_10
Patent number
US06300352B1

Reaction notes

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