Methanol → 2-[2-Fluoro-4-(4-methanesulfonyloxy-cyclohexyl)-phenyl]-1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester

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Reaction Steps

To a solution of 2-[2-fluoro-4-(4-hydroxy-cyclohexyl)-phenyl]-1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester (530 mg, 1.18 mmol) in DCM (8 mL) was added Et3N (179 mg, 0.3 mL, 1.77 mmol, 1.5 equiv.). The solution was cooled to an ice-water bath and then de-aerated by vacuum/nitrogen exchange. To this solution was transferred a solution of methanesulfonyl chloride (202 mg, 1.77 mmol, 1.5 equiv.) in DCM (2 mL). The clear solution was stirred with the ice-water bath on all the time for 1 h. TLC (5% MeOH in DCM indicated that the reaction was complete. The reaction was quenched by diluting with DCM (10 mL), followed by addition of NaHCO3 aq. (5 mL). The two layers were separated and the aqueous layer was extracted with DCM (2×5 mL). The combined extracts were washed with NaHCO3 aq. (5 mL), brine (5 mL) and dried (K2CO3). The solution was filtered through a silica gel pad, eluted with 5% MeOH in DCM. The filtrate was concentrated to dryness and purified again on a silica gel column, eluted with 5% MeOH in DCM to eliminate the minor component to afford 0.4 g (64% yield) of the title compound as an off-white wax-like solid material.

Provenance & Evidence