4-Methylmorpholine → (S)-benzyl 2-(2-morpholinoacetamido)propanoate

To DMTMM (76.1 g, 0.276 mol) and N-methylmorpholine (NMM; 32.9 mL, 0.300 mol) was added to a 0° C. solution of 2-morpholinoacetic acid (20.0 g, 0.138 mmol) and L-alanine benzyl ester hydrochloride (35.7 g, 0.166 mol) in DMF (100 mL) and DCM (200 mL). The reaction mixture was stirred for 4 h at ambient temperature then concentrated. EtOAc (500 mL) and water (500 mL) was added to the residue. The resulting two layers were separated and the aqueous phase was extracted with EtOAc (3×300 mL). The combined organic layers were washed with brine (3×500 mL), dried over anhydrous sodium sulfate, and concentrated. The residue was purified by flash column chromatography on silica gel (DCM/MeOH=100:3) to afford (S)-benzyl 2-(2-morpholinoacetamido)propanoate (21.1 g, 50% yield).

1. concentrationthen concentrated
2. additionEtOAc (500 mL) and water (500 mL) was added to the residue
3. customThe resulting two layers were separated
4. extractionthe aqueous phase was extracted with EtOAc (3×300 mL)
5. washThe combined organic layers were washed with brine (3×500 mL)
6. dry with materialdried over anhydrous sodium sulfate
7. concentrationconcentrated
8. customThe residue was purified by flash column chromatography on silica gel (DCM/MeOH=100:3)

ORD record

ord-0ba05b0e9cb44a6b98f64f4e6600feba

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09434761B2