Lithium hydroxide, monohydrate → L-Proline, N-(methoxycarbonyl)-L-valyl-5-methyl-, (5S)-

HRID 1625509Notes

Reaction equation

HRID 1625509 reaction equation
[CH3:1][O:2][C:3]([NH:5][C@@H:6]([CH:20]([CH3:22])[CH3:21])[C:7]([N:9]1[C@@H:13]([CH3:14])[CH2:12][CH2:11][C@H:10]1[C:15]([O:17]CC)=[O:16])=[O:8])=[O:4].O.[OH-].[Li+]>C(O)C>[CH3:1][O:2][C:3]([NH:5][C@@H:6]([CH:20]([CH3:22])[CH3:21])[C:7]([N:9]1[C@@H:13]([CH3:14])[CH2:12][CH2:11][C@H:10]1[C:15]([OH:17])=[O:16])=[O:8])=[O:4]

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 67411636(2S,5S)-ethyl 1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-5-methylpyrrolidine-2-carboxylate

Product 1

HCID 67412687L-Proline, N-(methoxycarbonyl)-L-valyl-5-methyl-, (5S)-Yield 98.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To an ice-cold stirred solution of ethyl (2S,5S)-1-[(2S)-2-(methoxycarbonylamino)-3-methyl-butanoyl]-5-methyl-pyrrolidine-2-carboxylate (5.6 g, 17.8 mmol) in ethanol (18 ml) is added a solution of lithium hydroxide monohydrate (17.8 mL of 1.7 M, 30.3 mmol). The reaction mixture is stirred for 5 hours at rt. The reaction mixture is concentrated, diluted with water, washed with ether. The aqueous solution is acidified with aq. 1N HCl, extracted with CH2Cl2. The combined extracts are washed with brine, dried (Na2SO4), concentrated to afford (2S,5S)-1-[(2S)-2-(methoxycarbonylamino)-3-methyl-butanoyl]-5-methyl-pyrrolidine-2-carboxylic acid (5 g, 94%) as a white solid.

Workup

  1. concentrationThe reaction mixture is concentrated
  2. additiondiluted with water
  3. washwashed with ether
  4. extractionextracted with CH2Cl2
  5. washThe combined extracts are washed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-0245b5327b75455c9b3ebb6ffeed14d8
Source dataset
uspto-grants-2014_07
Patent number
US08779156B2

Reaction notes

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