Реакция #2275696

Уравнение реакции

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

diisopropylethylamine

1-(3-dimethylaminopropyl)-3-ethylcarbodiimide

1-hydroxybenzotriazole

glycine methyl ester hydrochloride

→

desired product

Выход 40.0%

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

Выход 40.0%

Растворители

DMF

Условия реакции

Обработка

1. 1
   workup.STIRRINGstirred 3 days
2. 2
   КонцентрированиеThe reaction volume is partially concentrated under reduced pressure
3. 3
   workup.ADDITIONthen diluted with EtOAc
4. 4
   Промывкаwashed with saturated aqueous NaHCO3 and saturated aqueous NaCl
5. 5
   СушкаThe organic layer is dried (MgSO4)
6. 6
   Фильтрацияfiltered
7. 7
   Концентрированиеconcentrated under reduced pressure
8. 8
   Другоеto afford a yellow oil that
9. 9
   Другоеis purified over silica (EtOAc:heptane gradient 1:1 to 1:0)

Методика

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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