Lithium Hydroxide → 5-Methylpyrrolidine-2-carboxylic acid

HRID 590658Notes

Reaction equation

HRID 590658 reaction equation
COC(N[C@@H](C(C)C)C([N:9]1[C@@H:13]([CH3:14])[CH2:12][CH2:11][C@H:10]1[C:15]([O:17]CC)=[O:16])=O)=O.[Li+].[OH-]>CO>[CH3:14][CH:13]1[NH:9][CH:10]([C:15]([OH:17])=[O:16])[CH2:11][CH2:12]1

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 67411636(2S,5S)-ethyl 1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-5-methylpyrrolidine-2-carboxylate

Product 1

HCID 4088125-Methylpyrrolidine-2-carboxylic acidYield 56%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

(2S,5S)-Ethyl 1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-5-methylpyrrolidine-2-carboxylate (39.3 mmol, assuming complete conversion from the previous transformation) was suspended in MeOH (200 mL) and aqueous LiOH (1.0 M, 100 mL, 100 mmol) was added. The reaction mixture was stirred o/n, then concentrated under reduced pressure to remove most of the MeOH. The aqueous solution was washed 2× with DCM before being acidified to pH˜1-2 with 10% HCl. The acidic aqueous phase was then extracted 5× with EtOAc. The combined EtOAc extracts were dried over MgSO4 filtered and concentrated under reduced pressure to afford (2S,5S)-1-(S)-2-(Methoxycarbonylamino)-3-methylbutanoyl)-5-methylpyrrolidine-2-carboxylic acid (6.89 g, 56% over 2 steps).

Workup

  1. concentrationthen concentrated under reduced pressure
  2. customto remove most of the MeOH
  3. washThe aqueous solution was washed 2× with DCM
  4. extractionThe acidic aqueous phase was then extracted 5× with EtOAc
  5. dry with materialThe combined EtOAc extracts were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-89dd06b09ee644e2abc40cf25117fc56
Source dataset
uspto-grants-2016_01
Patent number
US09233974B2

Reaction notes

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