Pyridine → HCID 21727263, compound

HRID 1883945Notes

Reaction equation

HRID 1883945 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[C:8]([O:10][CH2:11][CH:12]([CH3:14])[CH3:13])=[O:9].[C:15]1([Mg]Cl)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.S(=O)(=O)(O)O>[Cu]I.C1COCC1>[CH2:11]([O:10][C:8]([N:1]1[CH:6]=[CH:5][CH:4]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:3]=[CH:2]1)=[O:9])[CH:12]([CH3:14])[CH3:13]

Participants

7

Reactant 4

HCID 1049PyridineHCID 1118Sulfuric AcidHCID 62365Isobutyl chloroformateHCID 178478979HCID 178478979, compound

Product 1

HCID 21727263HCID 21727263, compoundYield 85.2%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8028TetrahydrofuranSolvent3×

Procedure

1.9 g (0.01 mole) of CuI was added to a mixture of 18.7 g (0.236 mole) of pyridine and 150 ml of tetrahydrofuran under a N2 atmosphere, with stirring. The mixture was stirred at room temperature until the mixture became a homogeneous solution, and thereafter a solution of 28.7 g (0.21 mole) of isobutyl chloroformate and 20 ml of tetrahydrofuran was added dropwise, on an ice bath, so that the inner temperature of the reactor could not exceed 20° C. Further, 100 ml of 2M phenyl magnesium chloride solution (0.2 mole; a THF solution) was added to the mixture dropwise, over 1 hour, at the inner temperature of 0±3° C. (i.e., −3° C. to 3° C.). The mixture was stirred for 20 minutes at the temperature of 0±3° C., and further stirred for 1 hour 25° C. After removing about 60 ml of tetrahydrofuran by vacuum distillation, 180 ml of toluene was added, and then 60 g (0.061 mole) of 10% sulfuric acid was added dropwise. The resulting precipitate was removed by filtration through celite, and then the celite was washed with 40 ml of toluene. After removing the aqueous layer of the filtrate, the organic layer of the filtrate was washed twice with 180 ml each of 10% hydrochloric acid, and twice with 180 ml each of water. The organic layer was concentrated under a reduced pressure to obtain Compound I-2: obtained amount 51.0 g; purity 86.0% (determined by HPLC); yield 85.2%.

Workup

  1. stirringThe mixture was stirred at room temperature until the mixture
  2. customexceed 20° C
  3. customat the inner temperature of 0±3° C. (i.e., −3° C. to 3° C.)
  4. stirringThe mixture was stirred for 20 minutes at the temperature of 0±3° C.
  5. stirringfurther stirred for 1 hour 25° C
  6. customAfter removing about 60 ml of tetrahydrofuran
  7. distillationby vacuum distillation, 180 ml of toluene
  8. additionwas added
  9. customThe resulting precipitate was removed by filtration through celite
  10. washthe celite was washed with 40 ml of toluene
  11. customAfter removing the aqueous layer of the filtrate
  12. washthe organic layer of the filtrate was washed twice with 180 ml each of 10% hydrochloric acid
  13. concentrationThe organic layer was concentrated under a reduced pressure
  14. customto obtain Compound I-2
  15. customobtained amount 51.0 g

Sources & evidence

ORD record
ord-78eb8640dcf4499f936c7d7c7e10d8c8
Source dataset
uspto-grants-2004_07
Patent number
US06762303B2

Reaction notes

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