Reaction #2275705

Reaction equation

3,5-bis-benzyloxy-pyridine-2-carboxylic acid

1-(3-dimethylaminopropyl)-3-ethylcarbodiimide

1-hydroxybenzotriazole

α-aminoisobutyric acid

diisopropylethyl-amine

→

desired compound

Yield 45.0%

2-[(3,5-bis-benzyloxy-pyridine-2-carbonyl)-amino]-2-methyl-propionic acid methyl ester

Yield 45.0%

Solvents

DMF

Conditions

Workup

1. 1
   workup.ADDITIONare added
2. 2
   Concentrationthen concentrated under reduced pressure
3. 3
   OtherThe resulting brown oil is purified over silica (EtOAc:heptane 1:1)

Procedure

To a solution of 3,5-bis-benzyloxy-pyridine-2-carboxylic acid, 2, (1.0 g, 2.99 mmol) in DMF (20 mL) at room temperature under N2 is added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI) (0.925 g, 5.97 mmol) and 1-hydroxybenzotriazole (HOBt) (0.806 g, 5.97 mmol). The mixture is stirred for 15 minutes after which α-aminoisobutyric acid (0.917 g, 5.97 mmol) and diisopropylethyl-amine (DIPEA) (1.56 mL, 8.96 mmol) are added. The resulting solution is stirred at room temperature for 16 hours then concentrated under reduced pressure. The resulting brown oil is purified over silica (EtOAc:heptane 1:1) to afford 0.58 g (45% yield) of the desired compound as a colorless solid. 1H NMR (250 MHz, CDCl3) δ ppm 8.13 (1H, s), 8.02 (1H, d, J=2.3 Hz), 7.31-7.48 (10H, m), 6.90 (1H, d, J=2.3 Hz), 5.19 (2H, s), 5.10 (2H, s), 3.74 (3H, s), 1.58 (6H, s). HPLC-MS: m/z 435 [M+H]+.

Source