Hydrochloric Acid → (S)-benzyl (3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl)carbamate

Temperature

-40 °C

N-Benzyloxycarbonyl tert-leucine (24.7 mmol, 6.56 g) was taken up in dry THF (50 ml) and the solution cooled to -40° C. under a nitrogen atmosphere. Ethyl chloroformate (26 mmol, 2.84 g) was added and the solution left to stir for 10 min. N-methylmorpholine (52 mmol, 5.24 g) was added and the solution stirred for 50 min between -20° C. and -40° C. before adding neat methylamine hydrochloride (24.7 mmol, 1.67 g). The solution was allowed to warm to RT and stirred at this temperature for 18 hr. The solution was poured into 10% HCl (50 ml), extracted with EtOAc (50 ml×3), the combined organic layer washed with saturated sodium bicarbonate solution (1×55 ml), then brine (1×50 ml), dried (MgSO4) and the solvent removed in vacuo to give the title compound (5.72 g) as an off-white solid. δH (CDCl3) 1.0 (9H, s), 2.75 (3H, d), 3.6 (1H, d), 5.0-5.1 (2H, m), 5.65 (1H, d), 6.25 (1H, s), 7.25-7.4 (5H, m) and 8.0 (1H, s).

1. waitthe solution left
2. stirringthe solution stirred for 50 min between -20° C. and -40° C.
3. temperatureto warm to RT
4. stirringstirred at this temperature for 18 hr
5. extractionextracted with EtOAc (50 ml×3)
6. washthe combined organic layer washed with saturated sodium bicarbonate solution (1×55 ml)
7. dry with materialbrine (1×50 ml), dried (MgSO4)
8. customthe solvent removed in vacuo

ORD record

ord-afcac3992326495a93b0c7f233f8f092

Source dataset

uspto-grants-1998_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05827890