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

(2S,5 S)-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).

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

ORD record

ord-3580feded35f44b9899dfee3988ff9d8

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08921341B2