N-tert-Butoxycarbonyl or N-Boc

Protection

To a mixture of racemic trans-benzyl 3-amino-4-hydroxypyrrolidine-1-carboxylate (2.67 g, 11.30 mmol) and di-tert-butyl dicarbonate (3.70 g, 16.95 mmol) in CH2Cl2 (50 mL) was added Et3N (4.73 mL, 33.90 mmol) at 0°C. The mixture was then stirred at rt for 48 h. The reaction mixture was then conc., in vacuo giving a residue which was purified via silica gel chromatography (40% to 90% ethyl acetate/hexane) to yield a white solid as (±)-benzyl 3-(tert-butoxycarbonylamino)-4-hydroxypyrrolidine-1-carboxylate (3.36 g, 88 %).

 

Patent reference: WO2010001169 (Astrazeneca)

Deprotection

4 N HCI in dioxane (5 ml, 20 mmol) was added to a solution of tert-butyl 2-(3-{[5-(trifluoromethyl)pyridin-2- yl]oxy}phenyl)-7-azaspiro[3.5]nonane-7-carboxylate (888 mg, 1.92 mmol) in methylene chloride (15 ml) at room temp. After 1 h, the reaction mixture was concentrated in vacuo and dried under vacuum to give the title compound as a white solid (703 mg, 92%).

 

Patent reference: WO2010049841 (Pfizer)

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