1-Hydroxybenzotriazole → Benzyl (S)-3-(4-methoxyphenyl)-2-((S)-2-(2-morpholinoacetamido)propanamido)propanoate

To a solution of (S)-benzyl 2-((S)-2-aminopropanamido)-3-(4-methoxyphenyl)propanoate (HCl salt, 21.0 g, 53.5 mmol) in DMF (200 mL) at 0° C. was added HBTU (30.4 g, 80.3 mmol) and HOBt (10.8 g, 80.3 mmol). The mixture was stirred for 5 min then 2-morpholinoacetic acid (8.15 g, 56.2 mmol) and DIEA (46.5 mL, 214 mmol) were added. The reaction mixture was stirred at ambient temperature for 30 min. Saturated aqueous NaHCO3 (200 mL) was then added and the resulting mixture was extracted with EtOAc (300 mL×2). The combined extracts were washed with brine (400 mL), dried over anhydrous sodium sulfate, and concentrated. Purification of the residue by flash column chromatography on silica gel (heptane to EtOAc/heptane=3:2) afforded (S)-benzyl 3-(4-methoxyphenyl)-2-((S)-2-(2-morpholinoacetamido)propanamido)propanoate (23.0 g, 89% yield) as a colorless solid.

1. stirringThe reaction mixture was stirred at ambient temperature for 30 min
2. extractionthe resulting mixture was extracted with EtOAc (300 mL×2)
3. washThe combined extracts were washed with brine (400 mL)
4. dry with materialdried over anhydrous sodium sulfate
5. concentrationconcentrated
6. customPurification of the residue by flash column chromatography on silica gel (heptane to EtOAc/heptane=3:2)

ORD 기록

ord-e9ae184a612a46c3a79556cdcc48bb7f

출처 데이터셋

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09434761B2