Lithium hydroxide, monohydrate → (2S,4S)-1-(tert-butoxycarbonyl)-4-cyanopyrrolidine-2-carboxylic acid

HRID 1527318Notes

Reaction equation

HRID 1527318 reaction equation
C[O:2][C:3](=[O:18])[C@@H:4]1[CH2:8][C@H:7]([C:9]#[N:10])[CH2:6][N:5]1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12].O[Li].O>CO>[C:14]([O:13][C:11]([N:5]1[CH2:6][C@@H:7]([C:9]#[N:10])[CH2:8][C@H:4]1[C:3]([OH:18])=[O:2])=[O:12])([CH3:17])([CH3:15])[CH3:16]

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrate2×HCID 177504541,2-Pyrrolidinedicarboxylic acid, 4-cyano-, 1-(1,1-dimethylethyl) 2-methyl ester, (2S,4S)-

Product 1

HCID 14842641(2S,4S)-1-(tert-butoxycarbonyl)-4-cyanopyrrolidine-2-carboxylic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of N-boc-cis-4-cyano-L-proline methyl ester (800 mg, 3.15 mmol) in MeOH (27 mL) was cooled to 0° C. and LiOH.H2O (792 mg, 18.9 mmol) was added. The colorless solution was allowed to reach RT and stirred for 4 h. LiOH.H2O (792 mg, 18.9 mmol) was added and the reaction further stirred at for 1 hour to complete the reaction. MeOH was concentrated and the residue diluted in CH2Cl2 and treated with aqueous 1M HCl adjusting the pH to 1. The layers were separated and the aqueous one re-extracted with CH2Cl2 (×2). The combined organic extracts were dried (Na2SO4), filtered and concentrated to give the desired compound which was used in the next step without further purification. MS (LC/MS): 263.0 [M+Na]+, 503.2 [2M+Na]+, 239.1 [M−H]−.

Workup

  1. customto reach RT
  2. customthe reaction
  3. stirringfurther stirred at for 1 hour
  4. customthe reaction
  5. concentrationMeOH was concentrated
  6. additionthe residue diluted in CH2Cl2
  7. additiontreated with aqueous 1M HCl adjusting the pH to 1
  8. customThe layers were separated
  9. extractionthe aqueous one re-extracted with CH2Cl2 (×2)
  10. dry with materialThe combined organic extracts were dried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-4f7ab5fc984b4e40965166e7fc56158d
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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