Reaction #2275703

Reaction equation

4′-chloro-3-methoxy-biphenyl-4-carboxylic acid

glycine ethyl ester hydrochloride

1-(3-dimethylamino-propyl)-3-ethylcarbodiimide

1-hydroxybenzotriazole

diisopropylethylamine

→

desired product

Yield 85.0%

[(4′-chloro-3-methoxy-biphenyl-4-carbonyl)-amino]-acetic acid ethyl ester

Yield 85.0%

Solvents

EtOAc

CH2Cl2

DMF

Conditions

Workup

1. 1
   Washwashed with 1M HCl, 1M NaOH and saturated aqueous NaCl
2. 2
   OtherThe organic phase is separated
3. 3
   Dryingdried (MgSO4)
4. 4
   Filtrationfiltered
5. 5
   Concentrationconcentrated under reduced pressure
6. 6
   OtherThe crude material is purified over silica (hexanes:EtOAc 1:1)

Procedure

To a solution of 4′-chloro-3-methoxy-biphenyl-4-carboxylic acid, 9, (0.325 g, 1.24 mmol) in CH2Cl2 (5 mL) and DMF (1.5 mL) at room temperature under N2 is added glycine ethyl ester hydrochloride (0.19 g, 1.36 mmol), 1-(3-dimethylamino-propyl)-3-ethylcarbodiimide (EDCI) (0.261 g, 1.36 mmol), 1-hydroxybenzotriazole (HOBt) (0.033 g, 0.248 mmol) and diisopropylethylamine (DIPEA) (0.432 ml, 2.28 mmol). The resulting suspension is stirred for 16 hours after which the reaction mixture is diluted with EtOAc and washed with 1M HCl, 1M NaOH and saturated aqueous NaCl. The organic phase is separated, dried (MgSO4), filtered and concentrated under reduced pressure. The crude material is purified over silica (hexanes:EtOAc 1:1) to afford 0.364 g (85% yield) of the desired product as a colorless solid. 1H NMR (400 MHz, CDCl3) δ ppm 8.51 (1H, br s), 8.28 (1H, d, J=8.1 Hz), 7.53-7.57 (2H, m), 7.42-7.46 (2H, m), 7.27 (1H, dd, J=8.1, 1.6 Hz), 7.14 (1H, d, J=1.5 Hz), 4.29 (2H, d, J=4.8 Hz), 4.28 (2H, q, J=7.1 Hz), 4.09 (3H, s), 1.34 (3H, t, J=7.2 Hz). HPLC-MS: m/z 348 [M+H]+.

Source