Reaction #87095

Reaction equation

N-methylmorpholine

2-(4-hydroxypiperidin-1-yl)acetic acid

(S)-benzyl 2-((S)-2-aminopropanamido)-3-(4-methoxyphenyl)propanoate

HATU

→

(S)-benzyl 2-((S)-2-(2-(4-hydroxypiperidin-1-yl)acetamido)propanamido)-3-(4-methoxyphenyl)propanoate

Yield 87.0%

Solvents

dichloromethane

Water

Conditions

Workup

1. 1
   Extractionthe resulting mixture was extracted with dichloromethane (30 mL×3)
2. 2
   Dryingdried over anhydrous sodium sulfate
3. 3
   Concentrationconcentrated
4. 4
   OtherThe residue was purified by flash column chromatography on silica gel (petroleum ether/dichloromethane=5:1 to 1:1)

Procedure

To a solution of 2-(4-hydroxypiperidin-1-yl)acetic acid (0.41 g, 2.6 mmol) and (S)-benzyl 2-((S)-2-aminopropanamido)-3-(4-methoxyphenyl)propanoate (HCl salt, 0.93 g, 2.6 mmol) in dichloromethane (30 mL) at 0° C. was added HATU (1.1 g, 2.9 mmol) followed by N-methylmorpholine (1.05 g, 10.4 mmol). The reaction mixture was allowed to warm to ambient temperature and stirred for 1 h. Water (30 mL) was added and the resulting mixture was extracted with dichloromethane (30 mL×3). The organic extracts were combined, dried over anhydrous sodium sulfate, and concentrated. The residue was purified by flash column chromatography on silica gel (petroleum ether/dichloromethane=5:1 to 1:1) to afford (S)-benzyl 2-((S)-2-(2-(4-hydroxypiperidin-1-yl)acetamido)propanamido)-3-(4-methoxyphenyl)propanoate (1.1 g, 87% yield) as a colorless solid.

Source