Sodium Carbonate → 4-[2-(4-Chloro-phenyl)-5,5-dimethyl-cyclohex-1-enylmethyl]-piperazine-1-carboxylic acid tert-butyl ester

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Reaction Conditions

Reaction Steps

To a degassed solution of 4-(2-bromo-5,5-dimethyl-cyclohex-1-enylmethyl)-piperazine-1-carboxylic acid tert-butyl ester (1.3 g, 3.36 mmol) and 4-chlorophenyl boronic acid (0.78 g, 5.04 mmol) in 2:1 MeOH/1,4-dioxane (20 ml) at rt was added a solution of 2M Na2CO3 (3.3 ml, 6.72 mmol). Nitrogen was bubbled through the mixture for 2 min and then PdCl2[dppf] (200 mg, 0.28 mmol) was added. The reaction flask was sealed and heated to 100° C. where it was maintained for 1 h. After this time the suspension was cooled to rt and filtered through Celite®. The collected solids were washed with additional dichloromethane and the combined filtrate and washings were concentrated under reduced pressure. Purification by column chromatography on silica eluting with 6% EtOAc/heptanes gave 4-[2-(4-chloro-phenyl)-5,5-dimethyl-cyclohex-1-enylmethyl]-piperazine-1-carboxylic acid tert-butyl ester (1.0 g, 71%). HPLC-MS 419, 421 [M+1]+.

Provenance & Evidence