Hydrochloric Acid → Allyl 1-(cyclopropylamino)-2-hydroxy-1-oxohexan-3-ylcarbamate

To a solution of (3S)-3-amino-N-cyclopropyl-2-hydroxyhexanamide (10 g, 53.7 mmol), DIEA (28 mL, 161 mmol, 3 eq.) in methylene chloride (250 mL) was added dropewise at 0° C. to a solution of allylchloroformate (6.8 mL, 64.4 mmol, 1.2 eq.) in DCM (50 mL). The reaction solution was warmed to room temperature and stirred for 4 hours. Water (300 mL) was then slowly added followed by aqueous HCl (1.0 N, 300 mL). The phases were separated and the organics washed with saturated aqueous NaHCO3 (300 mL), brine (300 mL), dried with MgSO4, filtered, and concentrated in vacuo. The resulting off-white solid was recrystallized from 30% hexanes in EtOAc (120 mL) to yield the title compound M1A as a white solid. The mother liquor was concentrated, in vacuo, and recrystallized from 50% hexanes in EtOAc to yield another 4.04 g of M1A. The mother liquor from the second recrystallization was concentrated in vacuo on Celite®, and the resulting Celite® plug was purified by flash chromatography (Isco Companion®, SiO2, DCM to 70% EtOAc in DCM) to give 1.46 g of M1A. The total amount of compound M1A was 13.4 g. (Rf≈0.40 in 1:1 DCM:EtOAc, CAM detection).

1. customThe phases were separated
2. washthe organics washed with saturated aqueous NaHCO3 (300 mL), brine (300 mL)
3. dry with materialdried with MgSO4
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe resulting off-white solid was recrystallized from 30% hexanes in EtOAc (120 mL)

ORD record

ord-bff82061141445a8bc2655a959941846

Source dataset

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08372873B2