Tetrahydrofuran → (S)-1-((S)-2-((Methoxycarbonyl)amino)-3-methylbutanoyl)pyrrolidine-2-carboxylic acid

HRID 1411383Notes

Reaction equation

HRID 1411383 reaction equation
[CH3:1][O:2][C:3]([NH:5][C@@H:6]([CH:24]([CH3:26])[CH3:25])[C:7]([N:9]1[CH2:13][CH2:12][CH2:11][C@H:10]1[C:14]([O:16]CC1C=CC=CC=1)=[O:15])=[O:8])=[O:4].C1COCC1>CCCCCCC>[CH3:1][O:2][C:3]([NH:5][C@@H:6]([CH:24]([CH3:26])[CH3:25])[C:7]([N:9]1[CH2:13][CH2:12][CH2:11][C@H:10]1[C:14]([OH:16])=[O:15])=[O:8])=[O:4]

Participants

4

Reactant 2

HCID 8028TetrahydrofuranHCID 67240149(S)-Benzyl 1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)pyrrolidine-2-carboxylate

Product 1

HCID 12071044(S)-1-((S)-2-((Methoxycarbonyl)amino)-3-methylbutanoyl)pyrrolidine-2-carboxylic acid

Reagents, catalysts & solvents 1

HCID 8900HeptaneSolvent

Procedure

(S)-Benzyl 1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)pyrrolidine-2-carboxylate (40 g) and 5% Pd/Alumina were charged to a Parr reactor followed by THF (160 mL). The reactor was sealed and purged with nitrogen (6×20 psig) followed by a hydrogen purge (6×30 psig). The reactor was pressurized to 30 psig with hydrogen and agitated at room temperature for approximately 15 hours. The resulting slurry was filtered through a GF/F filter and concentrated to approximately 135 g solution. Heptane (120 mL) was added, and the solution was stirred until solids formed. After an addition 2-3 hours, additional heptane (240 mL) was added drop-wise, the slurry was stirred for approximately 1 hour, then filtered. The solids were dried to afford the title compound (S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)pyrrolidine-2-carboxylic acid.

Workup

  1. customThe reactor was sealed
  2. custompurged with nitrogen (6×20 psig)
  3. custompurge (6×30 psig)
  4. filtrationThe resulting slurry was filtered through a GF/F
  5. filtrationfilter
  6. concentrationconcentrated to approximately 135 g solution
  7. additionHeptane (120 mL) was added
  8. stirringthe solution was stirred until solids
  9. customformed
  10. additionwas added drop-wise
  11. stirringthe slurry was stirred for approximately 1 hour
  12. filtrationfiltered
  13. customThe solids were dried

Sources & evidence

ORD record
ord-e66f66d5edac4eb68319f160c481bcb8
Source dataset
uspto-grants-2014_12
Patent number
US08921514B2

Reaction notes

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