Ammonia → HCID 15117247, compound

HRID 409502Notes

Reaction equation

HRID 409502 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][O:24][CH3:25])=[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][O:24][CH3:25])=[O:9])([CH3:6])([CH3:5])[CH3:4]

Participants

6

Reactant 4

HCID 222AmmoniaHCID 6386tert-ButanolHCID 3028194LithiumHCID 60009868HCID 60009868, compound

Product 1

HCID 15117247HCID 15117247, compoundYield 103.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In a flask purged with ammonia gas, about 40 mL of liquid ammonia is collected with ammonia condenser at −78° C. To the liquid ammonia is added portionwise lithium metal (46 mmol; 320 mg) at the same temperature. To the deep blue solution is added a solution of (2S,4R)-4-benzyloxy-2-methoxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (9.2 mmol; 3.1 g) and tert-butanol (18.4 mmol; 1.36 g) in THF (15 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, and 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, and concentrated under reduced pressure to give (2S,4R)-4-hydroxy-2-methoxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (2.2 g).

Workup

  1. customIn a flask purged with ammonia gas, about 40 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-2a7b05b2d6a349ee9cc6e0768f26e7a9
Source dataset
uspto-grants-2014_06
Patent number
US08759365B2

Reaction notes

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