Potassium Carbonate → 2-(4-Prop-2-ynyl-benzyloxy)-pyridine

HRID 77861Notes

Reaction equation

HRID 77861 reaction equation
C[Si]([C:5]#[CH:6])(C)C.C([Mg]Br)C.Cl[CH2:12][C:13]1[CH:26]=[CH:25][C:16]([CH2:17][O:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=2)=[CH:15][CH:14]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.CO.[Cu]Br>[CH2:12]([C:13]1[CH:26]=[CH:25][C:16]([CH2:17][O:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=2)=[CH:15][CH:14]=1)[C:5]#[CH:6]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 66111TrimethylsilylacetyleneHCID 592550952-(4-Chloromethyl-benzyloxy)-pyridine2×HCID 178418443HCID 178418443, compound

Product 1

HCID 592553112-(4-Prop-2-ynyl-benzyloxy)-pyridine

Reagents, catalysts & solvents 3

HCID 24593copper(I) bromideCatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
65 °C

Procedure

To a solution of trimethylsilyl acetylene (496 μL, 3.51 mmol) in tetrahydrofuran (15 mL) was added ethyl magnesium bromide (3 M diethyl ether solution, 1.09 mL, 3.28 mmol) under nitrogen atmosphere at room temperature, which was stirred for 30 minutes at 65° C. The reaction solution was cooled to room temperature, and copper (I) bromide (168 mg, 1.17 mmol) and 2-(4-chloromethyl-benzyloxy)-pyridine (548 mg, 2.34 mmol) manufactured in Manufacturing Example 30-1-1 were added thereto and stirred for 15 hours and 10 minutes at 65° C. The reaction solution was partitioned into saturated aqueous ammonium chloride solution and ethyl acetate at room temperature. The organic layer was washed with saturated aqueous sodium chloride, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under a reduced pressure. To a solution of the resulting residue in methanol (5 mL) and tetrahydrofuran (10 mL) was added potassium carbonate (647 mg, 4.68 mmol), which was stirred for 3 hours and 25 minutes at room temperature. The reaction solution was partitioned into water and ethyl acetate at room temperature. The organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate, and the solvent was evaporated under a reduced pressure. The residue was purified by silica gel column chromatography (heptane:ethyl acetate=20:1) to obtain a mixture of the title compound and 2-(4-chloromethyl-benzyloxy)-pyridine (448 mg, target purity 20%, 17%).

Workup

  1. temperatureThe reaction solution was cooled to room temperature
  2. additionwere added
  3. stirringstirred for 15 hours and 10 minutes at 65° C
  4. customThe reaction solution was partitioned into saturated aqueous ammonium chloride solution and ethyl acetate at room temperature
  5. washThe organic layer was washed with saturated aqueous sodium chloride
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customthe solvent was evaporated under a reduced pressure
  8. stirringwas stirred for 3 hours and 25 minutes at room temperature
  9. customThe reaction solution was partitioned into water and ethyl acetate at room temperature
  10. washThe organic layer was washed with saturated aqueous sodium chloride
  11. dry with materialdried over anhydrous magnesium sulfate
  12. customthe solvent was evaporated under a reduced pressure
  13. customThe residue was purified by silica gel column chromatography (heptane:ethyl acetate=20:1)
  14. customto obtain

Sources & evidence

ORD record
ord-3b4b409253ce45b1afdbf9b6d7ebb83b
Source dataset
uspto-grants-2014_09
Patent number
US08841327B2

Reaction notes

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