(S)-3-tert-Butoxycarbonylamino-2-hydroxy-pentanoic acid → (S)-2-Amino-1-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-butan-1-ol

Temperature

15 °C

A solution of (S)-3-tert-Butoxycarbonylamino-2-hydroxy-pentanoic acid (2.00 g, 8.57 mmol) and N-Hydroxy-cyclopropanecarboxamidine (1.03 g, 10.29 mmol) in dichloromethane (20 mL) was stirred at 0° C. and 1.25 equivalents of N-cyclohexylcarbodiimide-N′-methyl polystyrene (1.70 mmol/g, 6.30 g, 10.72 mmol) was added in portions. The reaction mixture stirred under nitrogen for three hours while warming to 15° C. The reaction mixture was filtered, the resin washed with dichloromethane and the filtrate evaporated under vacuum to dryness. [LC/MS m/z=338 (M+H+Na)] The residue was dissolved in tetrahydrofuran (20 mL) and heated in a microwave reactor (Smith Creator) at 160° C. for three minutes, cooled to room temperature and evaporated under vacuum to dryness. [LC/MS m/z=320 (M+H+Na)]. The residue was dissolved in dichloromethane (50 mL) and stirred at room temperature as a 50 mL solution of 50% trifluoroacetic acid in dichloromethane was added dropwise. After three hours the reaction was evaporated under vacuum to dryness and dissolved in 50 mL of dichloromethane again. Three equivalents of Silicycle triamine-3 was added and the mixture stirred at room temperature overnight. The mixture was filtered and washed with dichloromethane. Evaporate under vacuum to give 1.04 g (61% overall). [LC/MS m/z=198 (M+H)]

1. filtrationThe reaction mixture was filtered
2. washthe resin washed with dichloromethane
3. customthe filtrate evaporated under vacuum to dryness
4. dissolution[LC/MS m/z=338 (M+H+Na)] The residue was dissolved in tetrahydrofuran (20 mL)
5. temperatureheated in a microwave reactor (Smith Creator) at 160° C. for three minutes
6. temperaturecooled to room temperature
7. customevaporated under vacuum to dryness
8. dissolutionThe residue was dissolved in dichloromethane (50 mL)
9. stirringstirred at room temperature as a 50 mL solution of 50% trifluoroacetic acid in dichloromethane
10. additionwas added dropwise
11. customAfter three hours the reaction was evaporated under vacuum to dryness
12. dissolutiondissolved in 50 mL of dichloromethane again
13. additionThree equivalents of Silicycle triamine-3 was added
14. stirringthe mixture stirred at room temperature overnight
15. filtrationThe mixture was filtered
16. washwashed with dichloromethane
17. customEvaporate under vacuum
18. customto give 1.04 g (61% overall)

ORD record

ord-daa2604772b14fcd85f284cddccf5e10

Source dataset

uspto-grants-2006_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07030116B2