Dimethyl Sulfoxide → tert-butyl N-(4-oxocyclohexyl)carbamate

Participants

Reaction Conditions

Reaction Steps

0.494 ml of DMSO was slowly added dropwise to 10 ml of a methylene chloride solution containing 0.526 ml of oxalyl chloride under argon gas atmosphere at −78° C. After 15 minutes from the completion of the addition, 30 ml of a methylene chloride suspension containing trans-4-tert-butoxycarbonylaminocyclohexanol in was added dropwise, and further 30 minutes later, 2.52 ml of triethylamine was added thereto and the mixture was stirred at −78° C. for 30 minutes and at 0° C. for 15 minutes. An aqueous sodium bicarbonate solution was added to the reaction mixture and the mixture was extracted with chloroform. The extract was dried over anhydrous sodium sulfate, and then, the solvent was removed under reduced pressure. The resulting residue was suspended in a hexane-isopropyl ether mixed solvent and collected by filtration to obtain 0.903 g of 4-(tert-butoxycarbonylamino)cyclohexanone. (2) To 350 ml of a toluene solution containing 33.05 g of the compound obtained in the above (1) was added dropwise 313 ml of 1.0 M diisobutyl aluminum hydride-toluene solution at −78° C., and the mixture was stirred at the same temperature for 4 hours. After an excessive reagent was decomposed by adding 33 ml of methanol dropwise to the mixture, 100 ml of water was added thereto, and the mixture was stirred for 1 hour. The precipitated insolubles were removed by filtration. The organic layer of the filtrate was separated and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, the resulting residue was suspended in chloroform-isopropyl ether mixed solvent under heating and the insolubles were removed by filtration. The filtrate was concentrated, and then, the same operation was performed with isopropyl ether. The resulting filtrate was concentrated and the residue was purified by silica gel flash column chromatography (solvent: ethyl acetate-hexane (1:2 to 1:1)), and the obtained colorless crystals were further suspended in hexane-isopropyl ether mixed solvent under heating and subjected to filtration at 0° C. to obtain 6.95 g of cis-4-tert-butoxycarbonylaminocyclohexanol. (3) The compounds of Reference Examples 9-58 to 9-64 in Table 6 were obtained in the same manner as in Reference Example 9-1, using the above-obtained cis-4-tert-butoxycarbonylaminocyclohexanol and the corresponding starting materials.

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