Реакция #2275703

Уравнение реакции

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

glycine ethyl ester hydrochloride

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

1-hydroxybenzotriazole

diisopropylethylamine

→

desired product

Выход 85.0%

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

Выход 85.0%

Растворители

EtOAc

CH2Cl2

DMF

Условия реакции

Обработка

1. 1
   Промывкаwashed with 1M HCl, 1M NaOH and saturated aqueous NaCl
2. 2
   ДругоеThe organic phase is separated
3. 3
   Сушкаdried (MgSO4)
4. 4
   Фильтрацияfiltered
5. 5
   Концентрированиеconcentrated under reduced pressure
6. 6
   ДругоеThe crude material is purified over silica (hexanes:EtOAc 1:1)

Методика

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]+.

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