benzyloxycarbonyl-L-valyl-L-proline t-butyl ester → tert-butyl (2S)-1-[(2S)-2-amino-3-methylbutanoyl]pyrrolidine-2-carboxylate

A solution of benzyloxycarbonyl-L-valyl-L-proline t-butyl ester (51.8 g) dissolved in absolute ethanol (1 liter) was placed in a 2 liter hydrogenation bottle. The reaction mixture was purged with nitrogen, and 10% (w/w) palladium on carbon catalyst (10 g, 50% (w/w) water wet) was added. The reaction was placed on a large shaker apparatus and shaken at room temperature under a hydrogen atmosphere (3.4 bar). After 1 h, hydrogen uptake ceased. The reaction mixture was checked by TLC [chloroform:ethyl acetate (85:15)] and shown to contain considerable starting material (Rf =0.55). Fresh catalyst (10 g) was added, and the reaction was placed back on the apparatus for another 4 h, at which point hydrogen uptake ceased. TLC of the reaction mixture showed complete absence of starting material. The reaction mixture was filtered through a pad of diatomaceous earth, and the filter cake was washed with ethanol. Evaporation of the ethanol from the condensed solution left a cloudy yellow oil. This oil was dissolved in ether (1 liter), filtered to remove a small amount of precipitate (dicyclohexylurea) and evaporated to give crude L-valyl-L-proline t-butyl ester as a yellow oil (32.1 g, 93%).

1. customThe reaction mixture was purged with nitrogen, and 10% (w/w) palladium on carbon catalyst (10 g, 50% (w/w) water wet)
2. additionwas added
3. additionFresh catalyst (10 g) was added
4. waitthe reaction was placed back on the apparatus for another 4 h, at which
5. filtrationThe reaction mixture was filtered through a pad of diatomaceous earth
6. washthe filter cake was washed with ethanol
7. customEvaporation of the ethanol from the condensed solution
8. waitleft a cloudy yellow oil
9. dissolutionThis oil was dissolved in ether (1 liter)
10. filtrationfiltered
11. customto remove a small amount of precipitate (dicyclohexylurea)
12. customevaporated

ORD record

ord-4cc0a8198b7741568a1d874772589167

Source dataset

uspto-grants-1992_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05164371