Potassium Carbonate → Ethyl3-[(2-chloro-5-nitro-pyrimidin-4-yl)-cyclopentyl-amino]-2,2-dimethyl-propanoate

Participants

Reaction Steps

To a stirred clear colourless solution of Ethyl3-(cyclopentylamino)-2,2-dimethyl-propanoate (US 2004/0176380 A1; 29.8 g, 139.7 mmol) in the acetone (700 mL) at room temperature was added potassium carbonate (21.3 g, 153.7 mmol) followed by 2,4-dichloro-5-nitropyrimidine (Aldrich; 29.81 g, 153.7 mmol). The reaction mixture was stirred vigorously at room temperature overnight. Potassium carbonate (7.75 g, 56 mmol) was added stirring continued for a further 4 hours. The reaction mixture was concentrated in vacuo to low volume and partitioned between Ethyl Acetate (600 mL) and water (400 mL). Phases were separated and the aqueous phase re-extracted with Ethyl Acetate (1×200 ml, 1×100 ml). The combined organic extracts were dried using MgSO4 and evaporated to dryness The residue was dissolved in DCM (150 mL) and purified in two batches using a Biotage Flash 75 system with 400 g Si column, conditioned with 10% Ethyl Acetate in isohexane and eluted with 10% Ethyl Acetate in isohexane. Product containing fractions were combined and evaporated giving the title compound as a yellow oil which solidified on standing in a freezer (27.90 g 54%)

Provenance & Evidence