تفاعل #2275696

معادلة التفاعل

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

diisopropylethylamine

1-(3-dimethylaminopropyl)-3-ethylcarbodiimide

1-hydroxybenzotriazole

glycine methyl ester hydrochloride

→

desired product

المردود 40.0%

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

المردود 40.0%

المذيبات

DMF

ظروف التفاعل

المعالجة

1. 1
   workup.STIRRINGstirred 3 days
2. 2
   تركيزThe reaction volume is partially concentrated under reduced pressure
3. 3
   workup.ADDITIONthen diluted with EtOAc
4. 4
   غسيلwashed with saturated aqueous NaHCO3 and saturated aqueous NaCl
5. 5
   تجفيفThe organic layer is dried (MgSO4)
6. 6
   ترشيحfiltered
7. 7
   تركيزconcentrated under reduced pressure
8. 8
   أخرىto afford a yellow oil that
9. 9
   أخرىis purified over silica (EtOAc:heptane gradient 1:1 to 1:0)

الإجراء التجريبي

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]+.

المصدر