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0 °C

A solution of benzyl (1S,2S,4R)-4-(tert-butyldimethylsilyloxy)-2-((Z)-prop-1-enyl)cyclohexylcarbamate (0.3 g, 0.74 mmol) in 10 mL of 7:3 EtOH:EtOAc was charged with palladium hydroxide and stirred under hydrogen atmosphere for 22 h. The palladium was removed by filtration and the solution was charged with fresh palladium hydroxide before again being placed under hydrogen atmosphere (5 kg pressure). After 3 h, the mixture was filtered through celite with EtOAc washings and concentrated in vacuo. The residue was dissolved in DMF (3 mL) and the resultant solution was cooled to 0° C. before being charged successively with (S)-Cbz methionine (0.31 g, 1.1 mmol), N-methyl morpholine (0.24 mL, 2.2 mmol), and BOP reagent (0.48 g, 1.1 mmol). The reaction was slowly warmed to 30° C. and then stirred for 12 h before being quenched water. The mixture was extracted with EtOAc, and the combined organic phases were washed with brine, dried, filtered, and concentrated in vacuo. The residue was purified by flash chromatography to afford benzyl (S)-1-((1S,2R,4R)-4-(tert-butyldimethylsilyloxy)-2-propylcyclohexylamino)-4-(methylthio)-1-oxobutan-2-ylcarbamate (0.25 g). blah, blah. MS found: (M+H)+=537.

1. customThe palladium was removed by filtration
2. additionthe solution was charged with fresh palladium hydroxide
3. waitAfter 3 h
4. filtrationthe mixture was filtered through celite with EtOAc washings
5. concentrationconcentrated in vacuo
6. dissolutionThe residue was dissolved in DMF (3 mL)
7. temperatureThe reaction was slowly warmed to 30° C.
8. stirringstirred for 12 h
9. custombefore being quenched water
10. extractionThe mixture was extracted with EtOAc
11. washthe combined organic phases were washed with brine
12. customdried
13. filtrationfiltered
14. concentrationconcentrated in vacuo
15. customThe residue was purified by flash chromatography