反応 #2275696

反応方程式

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

diisopropylethylamine

1-(3-dimethylaminopropyl)-3-ethylcarbodiimide

1-hydroxybenzotriazole

glycine methyl ester hydrochloride

→

desired product

収率 40.0%

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

収率 40.0%

溶媒

DMF

反応条件

後処理

1. 1
   workup.STIRRINGstirred 3 days
2. 2
   濃縮The reaction volume is partially concentrated under reduced pressure
3. 3
   workup.ADDITIONthen diluted with EtOAc
4. 4
   洗浄washed with saturated aqueous NaHCO3 and saturated aqueous NaCl
5. 5
   乾燥The organic layer is dried (MgSO4)
6. 6
   ろ過filtered
7. 7
   濃縮concentrated under reduced pressure
8. 8
   その他to afford a yellow oil that
9. 9
   その他is purified over silica (EtOAc:heptane gradient 1:1 to 1:0)

実験手順

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]+.

出典