Nitrogen → Benzyl (isobutylcarbamoyl)glycinate

Temperature

25 °C

Charge 3-methylbutanoic acid (106.36 g), toluene (800 ml) and triethylamine (126.46 g) into a 3-neck flask (R1). Heat R1 to 90° C. Add a solution of DPPA (289.3 g) in toluene (400 ml) slowly (Care: N2 released). Stir R1 at 90° C. for 30-60 mins, then cool to 20-30° C. In a separate flask (R2) charge benzyl 2-aminoacetate hydrochloride (200 g), triethylamine (150.54 g), and toluene (1000 ml) and stir at 20-30° C. for 1-2 hours. Add the R1 mixture into R2 drop wise slowly via addition funnel at 20-30° C. and stir for 1-2 hours. Slowly add the reaction mixture to water (2000 ml) with vigorous stirring. Separate the organic and extract the aqueous layer with EtOAc (2×1000 ml). Combine the organic layers and wash with 1 N hydrochloric acid (1000 ml), then 7% NaHCO3 aq (1000 ml), then water (1000 ml), then 15% brine (1000 ml). Concentrate under reduced pressure. Slurry the residue with heptane (1000 ml) then filter the solid. Dry the filter cake under reduced pressure below 40° C. to give benzyl 2-(isobutylcarbamoylamino)acetate (218g; 98.1% assay; 81.5% yield).

1. customto 90° C
2. additionAdd the R1 mixture into R2 drop
3. additionwise slowly via addition funnel at 20-30° C.
4. stirringstir for 1-2 hours
5. customSeparate the organic and
6. extractionextract the aqueous layer with EtOAc (2×1000 ml)
7. washCombine the organic layers and wash with 1 N hydrochloric acid (1000 ml)
8. concentrationConcentrate under reduced pressure
9. filtrationthen filter the solid
10. customDry the filter cake under reduced pressure below 40° C.

ORD record

ord-87dfe3dcd1c644038b815e6fbbb77bab

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09145437B2