3-Hydroxy-2,2,4,4-(tetramethoxy)cyclobutylcarbamate tert-butyl ester is a pharmaceutical intermediate, and there are literature reports that it can be used to prepare a novel androgen receptor antagonist.
Suspend (1r,3r)-3-amino-2,2,4,4-tetramethylcyclobutanol (79.6 mmol) in dioxane (240 ml). Add a solution of K2CO3 (164 mmol) in H2O (80 ml) dropwise to the reaction mixture at 0 °C. Stir the resulting mixture overnight at room temperature. Monitor the completion of reaction by TLC (2:1 Petroleum ether/EtOAc). Evaporate the reaction mixture. Dilute the residue with water (200 ml) and CH2Cl2 (400 ml). Separate the organic layer. Extract the aqueous layer with CH2Cl2 (100 ml x 3). Wash the combined organic layers with brine (100 ml). Dry the combined organic layers over Na2SO4. Filter the combined organic layers. Evaporate the combined organic layers. Purify the crude product by column chromatography (10:1 Petroleum ether/EtOAc) to obtain the trans-tert-Butyl 3-hydroxy-2,2,4,4-(tetraMethyl)cyclobutylcarbaMate.
