4-Methylmorpholine → HCID 86638959, compound

Temperature

0 °C

Ethyl chloroformate (0.441 ml, 4.59 mmol) was added slowly to a stirred solution of (4S)-5-tert-butoxy-5-oxo-4-({[2-(trimethylsilyl)ethoxy]carbonyl}amino) pentanoic acid (1.33 g, 3.83 mmol) and N-methylmorpholine (0.547 ml, 4.98 mmol) in THF (10 ml) at −20° C. A thick white solid precipitated from the solution and hindered stirring. THF (ca. 4 ml) was added to mobilise the suspension. The resulting mixture was stirred at −20° C. for 30 min, then allowed to warm slowly to 0° C. over the course of 2 h. The mixture was therefore stirred at 0° C. for a further 1 h. The slurry was filtered and the filtrate added portion wise over 30 min to a stirred solution of sodium borohydride (0.434 g, 11.48 mmol) in THF (4 ml) and water (1 ml) at 0° C. The mixture was quenched with NH4Cl solution, diluted with Et2O (50 ml) and the phases separated. The aqueous phase was extracted with Et2O (25 ml) and the combined organic phases were washed with NaHCO3 solution (25 ml) and brine (25 ml), dried (MgSO4) and evaporated to give tert-Butyl 5-hydroxy-N-{[2-(trimethylsilyl)ethoxy]carbonyl}-L-norvalinate (1.24 g) as a clear colourless oil.

1. customA thick white solid precipitated from the solution
2. additionTHF (ca. 4 ml) was added
3. stirringThe resulting mixture was stirred at −20° C. for 30 min
4. stirringThe mixture was therefore stirred at 0° C. for a further 1 h
5. filtrationThe slurry was filtered
6. customThe mixture was quenched with NH4Cl solution
7. additiondiluted with Et2O (50 ml)
8. customthe phases separated
9. extractionThe aqueous phase was extracted with Et2O (25 ml)
10. washthe combined organic phases were washed with NaHCO3 solution (25 ml) and brine (25 ml)
11. dry with materialdried (MgSO4)
12. customevaporated

ORD record

ord-cb3850fb2d744a5e9a68f7050381be4d

Source dataset

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08217050B2