Triethylamine → 1-Chloro-2-(4-ethynyl-benzyl)-4-(beta-D-glucopyranos-1-yl)-benzene

HRID 1890452Notes

Reaction equation

HRID 1890452 reaction equation
C(N([CH2:6][CH3:7])CC)C.C[Si](C#C)(C)C.[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([C@:21]2([O:30][C@H:29]([CH2:31][OH:32])[C@@H:27]([OH:28])[C@H:25]([OH:26])[C@H:23]2[OH:24])[OH:22])=[CH:17][C:16]=1[CH2:33][C:34]1[CH:39]=[CH:38][C:37](OS(C(F)(F)F)(=O)=O)=[CH:36][CH:35]=1.C(=O)([O-])O.[Na+]>CN(C)C=O.[Cu](I)I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([C@:21]2([O:30][C@H:29]([CH2:31][OH:32])[C@@H:27]([OH:28])[C@H:25]([OH:26])[C@H:23]2[OH:24])[OH:22])=[CH:17][C:16]=1[CH2:33][C:34]1[CH:35]=[CH:36][C:37]([C:6]#[CH:7])=[CH:38][CH:39]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 66111Trimethylsilylacetylene2×HCID 516892Sodium BicarbonateHCID 866006751-chloro-4-(beta-D-glucopyranos-1-yl)-2-(4-trifluoromethylsulfonyloxy-benzyl)-benzene

Product 1

HCID 866006811-Chloro-2-(4-ethynyl-benzyl)-4-(beta-D-glucopyranos-1-yl)-benzene

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 178418476HCID 178418476, compoundCatalyst2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

25 mg of copper iodide, 44 mg of bis-(triphenylphosphine)-palladium dichloride, 0.30 mL triethylamine and finally 0.14 mL of trimethylsilylacetylene are added under argon to a solution of 0.32 g 1-chloro-4-(β-D-glucopyranos-1-yl)-2-[4-(trifluoromethylsulphonyloxy)-benzyl]-benzene in 3 mL of dimethylformamide. The flask is tightly sealed and stirred for 8 h at 90° C. Then another 25 mg of bis-(triphenylphosphine)-palladium dichloride and 0.1 mL trimethylsilylacetylene are added, and the solution is stirred for a further 10 h at 90° C. Then aqueous sodium hydrogen carbonate solution is added, the resultant mixture is extracted three times with ethyl acetate, and the combined organic phases are dried over sodium sulfate. After the solvent has been eliminated the residue is dissolved in 5 mL of methanol and combined with 0.12 g potassium carbonate. The mixture is stirred for 1 h at ambient temperature and then neutralized with 1 M hydrochloric acid. Then the methanol is evaporated off, the residue is combined 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 through silica gel (dichloromethane/methanol 1:0->5:1).

Workup

  1. customThe flask is tightly sealed
  2. stirringthe solution is stirred for a further 10 h at 90° C
  3. extractionthe resultant mixture is extracted three times with ethyl acetate
  4. dry with materialthe combined organic phases are dried over sodium sulfate
  5. dissolutionis dissolved in 5 mL of methanol
  6. stirringThe mixture is stirred for 1 h at ambient temperature
  7. customThen the methanol is evaporated off
  8. extractionextracted with ethyl acetate
  9. customThe organic extracts collected
  10. dry with materialare dried over sodium sulfate
  11. customthe solvent is removed
  12. customThe residue is chromatographed through silica gel (dichloromethane/methanol 1:0->5:1)

Sources & evidence

ORD record
ord-b140f7f8dddb45f994d8c387f3b9b5e1
Source dataset
uspto-grants-2013_08
Patent number
US08507450B2

Reaction notes

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