反应详情

To a solution of (R)-3-[2-(tert-butoxycarbonyl-ethoxycarbonylmethyl-amino)-propionylamino]-4-(3′-chloro-biphenyl-4-yl)-butyric acid ethyl ester (290 mg, 0.504 mmol) in THF (3 ml) and MeOH (0.5 ml) at room temperature is added 2M NaOH (1.009 ml, 2.017 mmol). The reaction is stirred at room temperature over night. The mixture is concentrated to dryness and the crude i taken up in DCM (3.00 ml), to which is added TFA (3.89 ml, 50.4 mmol) and the mixture is stirred at room temperature for 2 hr. The reaction is concentrated for HPLC purification. Reverse phase HPLC [25 to 50% ACN—H2O (0.1% TFA) over 10 min by Sunfire C18 column] give (R)-3-[(S)-2-(Carboxymethyl-amino)-propionylamino]-4-(3′-chloro-biphenyl-4-yl)-butyric acid and (R)-3-[(R)-2-(Carboxymethyl-amino)-propionylamino]-4-(3′-chloro-biphenyl-4-yl)-butyric acid.

1. concentrationThe mixture is concentrated to dryness
2. stirringthe mixture is stirred at room temperature for 2 hr
3. concentrationThe reaction is concentrated for HPLC purification