Dicyclohexylamine → (S)-2-(Acetylthio)-4-methylpentanoic acid

Temperature

0 °C

Thioacetic acid (4.2 g, 54.4 mmol) and DMF (100 mL, 1.0 mol) were combined, and the mixture cooled in an ice bath. Sodium carbonate (5.8 g, 54.4 mmol) was added. After 30 minutes, (R)-2-bromo-4-methylpentanoic acid (10.1 g, 51.8 mmol) in DMF (20 mL) was added dropwise and the mixture was stirred at 0° C. to room temperature over 6 hours. The mixture was diluted with 100 mL EtOAc and extracted with 100 mL of a 1:1 1N HCl:saturated aqueous NaCl solution. The layers were separated and the aqueous phase was extracted with additional EtOAc (100 mL). The organics were combined, washed with saturated aqueous NaCl, dried over MgSO4, filtered, and concentrated under reduced pressure. The recovered oil was dissolved into diisopropyl ether (45 mL, 320 mmol) and chilled at 0° C. Dicyclohexylamine (10.1 mL, 50.7 mmol) was added dropwise and the solid was allowed to crash out of solution. After stirring for an additional 30 minutes the material was filtered and washed with 75 mL cold diisopropyl ether. The recovered solid (14 g) was suspended in 100 mL EtOAc. 150 mL of 5% KHSO4 was added and the layers were separated. The organic was washed with saturated aqueous NaCl, dried over MgSO4, filtered, and concentrated under reduced pressure. The recovered oil was then azeotroped (3×25 mL toluene) to yield the title compound (6.1 g) as a dicyclohexylamine salt.

1. temperaturethe mixture cooled in an ice bath
2. extractionextracted with 100 mL of a 1:1 1N HCl
3. customThe layers were separated
4. extractionthe aqueous phase was extracted with additional EtOAc (100 mL)
5. washwashed with saturated aqueous NaCl
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. stirringAfter stirring for an additional 30 minutes the material
10. filtrationwas filtered
11. washwashed with 75 mL cold diisopropyl ether
12. addition150 mL of 5% KHSO4 was added
13. customthe layers were separated
14. washThe organic was washed with saturated aqueous NaCl
15. dry with materialdried over MgSO4
16. filtrationfiltered
17. concentrationconcentrated under reduced pressure
18. customThe recovered oil was then azeotroped (3×25 mL toluene)

ORD record

ord-fbeed1f1c20d411faaa04d1d27c580b2

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08889882B2