Triethylamine → tert-butyl (2S,4R)-4-(2-cyano ethoxy)-2-[(dimethylamino)carbonyl]pyrrolidine-1-carboxylate

HRID 1662719Notes

Reaction equation

HRID 1662719 reaction equation
[CH3:1][N:2]([CH3:21])[C:3]([C@@H:5]1[CH2:9][C@@H:8]([O:10][CH2:11][CH2:12]O)[CH2:7][N:6]1[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[O:4].C[CH2:23][N:24](CC)CC.CS(Cl)(=O)=O.C([O-])(O)=O.[Na+]>C(Cl)(Cl)Cl>[C:23]([CH2:12][CH2:11][O:10][C@H:8]1[CH2:7][N:6]([C:14]([O:16][C:17]([CH3:18])([CH3:19])[CH3:20])=[O:15])[C@H:5]([C:3]([N:2]([CH3:1])[CH3:21])=[O:4])[CH2:9]1)#[N:24]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 516892Sodium BicarbonateHCID 67430889tert-butyl (2S,4R)-2-[(dimethylamino)carbonyl]-4-(2-hydroxyethoxy)pyrrolidine-1-carboxylate

Product 1

HCID 67430064tert-butyl (2S,4R)-4-(2-cyano ethoxy)-2-[(dimethylamino)carbonyl]pyrrolidine-1-carboxylateYield 39.5%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a solution of 3.00 g of the compound obtained in Step 143-2 and 2.01 g of Et3N in CHCl3 (30 ml) was added 1.36 g of methane sulfonyl chloride under ice cooling and the reaction mixture was stirred at room temperature for one hour. To the solution was added a saturated aqueous solution of NaHCO3 and the resulting mixture was extracted with EtOAc; the organic layer was washed with saturated brine and dried over Na2SO4, then, the drying agent was separated by filtration and the solvent was evaporated under reduced pressure. To a solution of the obtained residue in MeCN (40 ml) was added 2.58 g potassium cyanide and 260 mg of 18-crown-6-ether, and the reaction mixture was refluxed for two hours. To the solution was added water and the resulting mixture was extracted with EtOAc; the organic layer was washed with saturated brine and dried over Na2SO4, then, the drying agent was separated by filtration and the solvent was evaporated under reduced pressure. The obtained residue was purified by column chromatography (silicagel 60N; mobile phase: EtOAc) obtained 1.22 g of the title compound.

Workup

  1. extractionthe resulting mixture was extracted with EtOAc
  2. washthe organic layer was washed with saturated brine
  3. dry with materialdried over Na2SO4
  4. customthe drying agent was separated by filtration
  5. customthe solvent was evaporated under reduced pressure
  6. additionTo a solution of the obtained residue in MeCN (40 ml) was added 2.58 g potassium cyanide and 260 mg of 18-crown-6-ether
  7. temperaturethe reaction mixture was refluxed for two hours
  8. additionTo the solution was added water
  9. extractionthe resulting mixture was extracted with EtOAc
  10. washthe organic layer was washed with saturated brine
  11. dry with materialdried over Na2SO4
  12. customthe drying agent was separated by filtration
  13. customthe solvent was evaporated under reduced pressure
  14. customThe obtained residue was purified by column chromatography (silicagel 60N; mobile phase: EtOAc)

Sources & evidence

ORD record
ord-e751dd04981445c689c9435402b34203
Source dataset
uspto-grants-2011_10
Patent number
US08030499B2

Reaction notes

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