Reaktion #2275716

Reaktionsgleichung

3-hydroxypicolinic acid

diisopropylethylamine

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

EDCI

1-hydroxybenzotriazole

glycine tert-butyl ester HCl

→

desired compound

Ausbeute 22.0%

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

Ausbeute 22.0%

Lösungsmittel

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONis introduced
2. 2
   Einengenthen concentrated under reduced pressure
3. 3
   workup.ADDITIONThe reaction mixture is diluted with EtOAc
4. 4
   Waschenthen washed with 1M HCl, sat. NaCl
5. 5
   Trocknenthe organic layer is dried (MgSO4)
6. 6
   Filtrationfiltered
7. 7
   Einengenconcentrated under reduced pressure to a crude oil that
8. 8
   Sonstigeis purified over silica (EtOAc/heptane 1:4)

Vorschrift

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]+.

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