Dicyclohexylcarbodiimide → (S)-5-(1-amino-2-methylpropyl)-3-methyl-1,2,4-oxadiazole

A solution of BOC-L-valine (4.34 g, 20.0 mmol) in dichloromethane (20 mL) was cooled to 0° C. and treated dropwise with a solution of dicyclohexylcarbodiimide (2.06 g, 10.0 mmol) in dichloromethane (5 mL). After 1 hour the white solid which had formed was removed by filtration and the filtrate concentrated under reduced pressure. The residue was dissolved in pyridine (15 mL) and treated with acetamidoxime (488 mg, 6.6 mmol) in pyridine (5 mL) and the mixture heated at reflux for 1 hour. The pyridine was evaporated under reduced pressure and the residue partitioned between ethyl acetate and water. The organic phase was washed several times with water, dried over magnesium sulfate and concentrated. The residue was chromatographed on silica gel using 10% ethyl acetate in hexanes to elute the product (0.62 g, 25%) as a white solid.

1. customAfter 1 hour the white solid which had formed
2. customwas removed by filtration
3. concentrationthe filtrate concentrated under reduced pressure
4. dissolutionThe residue was dissolved in pyridine (15 mL)
5. temperaturethe mixture heated
6. temperatureat reflux for 1 hour
7. customThe pyridine was evaporated under reduced pressure
8. customthe residue partitioned between ethyl acetate and water
9. washThe organic phase was washed several times with water
10. dry with materialdried over magnesium sulfate
11. concentrationconcentrated
12. customThe residue was chromatographed on silica gel using 10% ethyl acetate in hexanes
13. washto elute the product (0.62 g, 25%) as a white solid

ORD record

ord-abb5f33c734f4035b72b3e61fdcd430b

Source dataset

uspto-grants-2004_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06835741B2