Ammonia → HCID 59810892, compound

HRID 409476Notes

Reaction equation

HRID 409476 reaction equation
N.[Li].[C:3]([O:7][C:8]([N:10]1[CH2:14][C@H:13]([O:15]CC2C=CC=CC=2)[CH2:12][C@H:11]1[CH2:23][CH3:24])=[O:9])([CH3:6])([CH3:5])[CH3:4].C(O)(C)(C)C>C1COCC1>[C:3]([O:7][C:8]([N:10]1[CH2:14][C@H:13]([OH:15])[CH2:12][C@H:11]1[CH2:23][CH3:24])=[O:9])([CH3:6])([CH3:5])[CH3:4]

Participants

6

Reactant 4

HCID 222AmmoniaHCID 6386tert-ButanolHCID 3028194LithiumHCID 59614418HCID 59614418, compound

Product 1

HCID 59810892HCID 59810892, compoundYield 99.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In a flask purged with ammonia gas, about 150 mL of liquid ammonia is collected with ammonia condenser at −78° C. To the liquid ammonia is added portion wise lithium metal (116 mmol; 805 mg) at the same temperature. To the deep blue solution is added a solution of (2R,4R)-4-benzyloxy-2-ethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (29.1 mmol; 8.90 g) and tert-butanol (58.2 mmol; 4.31 g) in THF (30 mL). After stirring for 2 hours, the reaction mixture is quenched with MeOH, and then warmed to ambient temperature. The mixture is diluted with water, then aqueous 1M HCl is added to reach pH 8-9. The product is extracted three times with EtOAc. The combined organic layer is washed with brine, dried over MgSO4, filtered, concentrated under reduced pressure to give (2R,4R)-4-hydroxy-2-ethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (6.25 g, 99.8%).

Workup

  1. customIn a flask purged with ammonia gas, about 150 mL of liquid ammonia
  2. customis collected with ammonia condenser at −78° C
  3. customthe reaction mixture is quenched with MeOH
  4. additionThe mixture is diluted with water
  5. additionaqueous 1M HCl is added
  6. extractionThe product is extracted three times with EtOAc
  7. washThe combined organic layer is washed with brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-cdb5dea78fee4cdba697a73ccdd517fa
Source dataset
uspto-grants-2014_06
Patent number
US08759365B2

Reaction notes

Loading…