반응 #2275696

반응 방정식

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

diisopropylethylamine

1-(3-dimethylaminopropyl)-3-ethylcarbodiimide

1-hydroxybenzotriazole

glycine methyl ester hydrochloride

→

desired product

수율 40.0%

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

수율 40.0%

용매

DMF

반응 조건

후처리

1. 1
   workup.STIRRINGstirred 3 days
2. 2
   농축The reaction volume is partially concentrated under reduced pressure
3. 3
   workup.ADDITIONthen diluted with EtOAc
4. 4
   세척washed with saturated aqueous NaHCO3 and saturated aqueous NaCl
5. 5
   건조The organic layer is dried (MgSO4)
6. 6
   여과filtered
7. 7
   농축concentrated under reduced pressure
8. 8
   기타to afford a yellow oil that
9. 9
   기타is purified over silica (EtOAc:heptane gradient 1:1 to 1:0)

실험 절차

To a solution of 3,5-bis-benzyloxy-pyridine-2-carboxylic acid HCl, 2, (8.06 g, 21.7 mmol) in DMF (100 mL) at 0° C. under N2 is added diisopropylethylamine (11.35 mL, 65.1 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI) (6.23 g, 32.6 mmol) and 1-hydroxybenzotriazole (HOBt) (0.294 g, 2.2 mmol). The solution is stirred for 5 minutes and glycine methyl ester hydrochloride (4.09 g, 32.6 mmol) is added. The reaction is allowed to warm slowly to room temperature and stirred 3 days. The reaction volume is partially concentrated under reduced pressure then diluted with EtOAc and washed with saturated aqueous NaHCO3 and saturated aqueous NaCl. The organic layer is dried (MgSO4), filtered and concentrated under reduced pressure to afford a yellow oil that is purified over silica (EtOAc:heptane gradient 1:1 to 1:0) to afford 3.5 g (40% yield) of the desired product as a yellow oil. 1H NMR (400 MHz, CDCl3) δ ppm 8.12 (1H, t, J=4.9 Hz), 7.95 (1H, d, J=1.8 Hz), 7.38-7.44 (2H, m), 7.22-7.35 (8H, m), 6.85 (1H, d, J=2.6 Hz), 5.14 (2H, s), 5.03 (2H, s), 4.18 (2H, d, J=5.5 Hz), 3.69 (3H, s). HPLC-MS: m/z 407 [M+H]+.

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