反応 #2275716

反応方程式

3-hydroxypicolinic acid

diisopropylethylamine

1-(3-dimethyl-aminopropyl)-3-ethylcarbodiimide

EDCI

1-hydroxybenzotriazole

glycine tert-butyl ester HCl

→

desired compound

収率 22.0%

[(3-hydroxy-pyridine-2-carbonyl)-amino]-acetic acid tert-butyl ester

収率 22.0%

溶媒

DMF

反応条件

後処理

1. 1
   workup.ADDITIONis introduced
2. 2
   濃縮then concentrated under reduced pressure
3. 3
   workup.ADDITIONThe reaction mixture is diluted with EtOAc
4. 4
   洗浄then washed with 1M HCl, sat. NaCl
5. 5
   乾燥the organic layer is dried (MgSO4)
6. 6
   ろ過filtered
7. 7
   濃縮concentrated under reduced pressure to a crude oil that
8. 8
   その他is purified over silica (EtOAc/heptane 1:4)

実験手順

To a solution of 3-hydroxypicolinic acid (0.20 g, 1.44 mmol) in DMF (5 mL) at 0° C. under N2 is added diisopropylethylamine (DIPEA) (0.75 ml, 4.3 mmol), 1-(3-dimethyl-aminopropyl)-3-ethylcarbodiimide (EDCI) (0.412 g, 2.9 mmol) and 1-hydroxybenzotriazole (HOBt) (0.019 g, 0.14 mmol). The resulting mixture is stirred for 5 min before glycine tert-butyl ester HCl (0.36 g, 2.9 mmol) is introduced. The resulting solution is stirred at room temperature for 3 days then concentrated under reduced pressure. The reaction mixture is diluted with EtOAc then washed with 1M HCl, sat. NaCl, and the organic layer is dried (MgSO4), filtered and concentrated under reduced pressure to a crude oil that is purified over silica (EtOAc/heptane 1:4) to afford 0.078 g (22% yield) of the desired compound as an off-white solid. 1H NMR (400 MHz, CDCl3) δ ppm 11.80 (1H, s), 8.39 (1H, br s), 8.02 (1H, dd, J=4.4, 1.5 Hz), 7.27 (1H, dd, J=8.8, 4.4 Hz), 7.25 (1H, dd, J=8.4, 1.5 Hz), 4.06 (2H, d, J=5.5 Hz), 1.44 (9H, s). HPLC-MS: m/z 197 [M-tBu]+.

出典