Reaction #2275696

Reaction equation

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

diisopropylethylamine

1-(3-dimethylaminopropyl)-3-ethylcarbodiimide

1-hydroxybenzotriazole

glycine methyl ester hydrochloride

→

desired product

Yield 40.0%

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

Yield 40.0%

Solvents

DMF

Conditions

Workup

1. 1
   workup.STIRRINGstirred 3 days
2. 2
   ConcentrationThe reaction volume is partially concentrated under reduced pressure
3. 3
   workup.ADDITIONthen diluted with EtOAc
4. 4
   Washwashed with saturated aqueous NaHCO3 and saturated aqueous NaCl
5. 5
   DryingThe organic layer is dried (MgSO4)
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated under reduced pressure
8. 8
   Otherto afford a yellow oil that
9. 9
   Otheris purified over silica (EtOAc:heptane gradient 1:1 to 1:0)

Procedure

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]+.

Source