Acetone → 2-(4-Cyclopropyl-benzyl)-4-(beta-D-glucopyranos-1-yl)-benzonitrile

HRID 1038355

Reaction equation

HRID 1038355 reaction equation
Br[CH2:2][C:3]1[CH:10]=[C:9]([C@:11]2([O:29][C@H:28]([CH2:30][O:31]C(=O)C)[C@@H:23]([O:24]C(=O)C)[C@H:18]([O:19]C(=O)C)[C@H:13]2[O:14]C(=O)C)[OH:12])[CH:8]=[CH:7][C:4]=1[C:5]#[N:6].[CH:35]1([C:38]2[CH:43]=[CH:42][C:41](B(O)O)=[CH:40][CH:39]=2)[CH2:37][CH2:36]1.C(=O)([O-])[O-].[K+].[K+].CC(C)=O>[Cl-].[Na+].O.[Pd](Cl)Cl.O>[CH:35]1([C:38]2[CH:43]=[CH:42][C:41]([CH2:2][C:3]3[CH:10]=[C:9]([C@:11]4([O:29][C@H:28]([CH2:30][OH:31])[C@@H:23]([OH:24])[C@H:18]([OH:19])[C@H:13]4[OH:14])[OH:12])[CH:8]=[CH:7][C:4]=3[C:5]#[N:6])=[CH:40][CH:39]=2)[CH2:37][CH2:36]1

Participants

8

Reactant 4

HCID 180AcetoneHCID 11430Potassium CarbonateHCID 28494284-Cyclopropylbenzeneboronic acidHCID 866564352-Bromomethyl-4-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranos-1-yl)-benzonitrile

Product 1

HCID 866564402-(4-Cyclopropyl-benzyl)-4-(beta-D-glucopyranos-1-yl)-benzonitrile

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 962WaterSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

An Ar filled flask is charged with a stir bar, 2-bromomethyl-4-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranos-1-yl)-benzonitrile (1.78 g), 4-cyclopropyl-phenylboronic acid (1.00 g), potassium carbonate (1.85 g) and a 3:1 mixture of degassed acetone and water (22 mL). The mixture is stirred at room temperature for 5 min, before it is cooled in an ice-bath. Then palladium dichloride (30 mg) is added and the reaction mixture is stirred for 16 h at ambient temperature. The mixture is then diluted with brine and extracted with ethyl acetate. The combined extracts are dried over sodium sulfate and the solvent is removed under reduced pressure. The residue is dissolved in methanol (20 mL) and treated with 4 M aqueous potassium hydroxide solution (3.8 mL). The resulting solution is stirred at ambient temperature for 1 h and then neutralized with 1 M hydrochloric acid. The methanol is evaporated, and the residue is diluted with brine and extracted with ethyl acetate. The organic extracts collected are dried over sodium sulfate, and the solvent is removed. The residue is chromatographed on silica gel (dichloromethane/methanol 1:0->8:1).

Workup

  1. additionAn Ar filled flask
  2. additionis charged with a stir bar
  3. temperatureis cooled in an ice-bath
  4. stirringthe reaction mixture is stirred for 16 h at ambient temperature
  5. extractionextracted with ethyl acetate
  6. dry with materialThe combined extracts are dried over sodium sulfate
  7. customthe solvent is removed under reduced pressure
  8. dissolutionThe residue is dissolved in methanol (20 mL)
  9. additiontreated with 4 M aqueous potassium hydroxide solution (3.8 mL)
  10. stirringThe resulting solution is stirred at ambient temperature for 1 h
  11. customThe methanol is evaporated
  12. additionthe residue is diluted with brine
  13. extractionextracted with ethyl acetate
  14. customThe organic extracts collected
  15. dry with materialare dried over sodium sulfate
  16. customthe solvent is removed
  17. customThe residue is chromatographed on silica gel (dichloromethane/methanol 1:0->8:1)

Sources & evidence

ORD record
ord-e399a88068594a7b94e8d185670c551d
Source dataset
uspto-grants-2013_10
Patent number
US08551957B2

Linked notes

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