Diethyl dithiophosphate, potassium salt → (5S)-1-azabicyclo[3.3.0]octane-3-carbothioamide

関与物質

反応手順

In 100 ml of 4N solution of hydrogen chloride in ethyl acetate, 5.10 g of a diastereomer mixture of (5S)-1-azabicyclo[3.3.0]octane-3-carbonitrile was dissolved. Then, 7 g of O,O-diethyl dithiophosphate was added, followed by stirring at room temperature for 16 hours. After the solvent was evaporated, the residue was washed with ethyl acetate, followed by drying under reduce pressure, whereby (5S)-1-azabicyclo[3.3.0]octane-3-carbothioamide was obtained. The resulting product was dissolved in 150 ml of isopropanol, 6.3 g of 2-bromo-1-indanone and 3.7 g of calcium carbonate were added, and the mixture was heated under reflux for 5 hours. After cooling, the insoluble matter was removed by filtration and the solvent was evaporated. To the resulting residue, ethyl acetate and 1N hydrochloric acid were added. The aqueous layer was separated, and neutralized with sodium bicarbonate, followed by extraction with chloroform. The extract was dried over anhydrous sodium sulfate. The solvent was evaporated, and the resulting residue was subjected to preparative medium-pressure column chromatography, whereby 0.32 g of a (3R,5S) form compound (Example 63A) and 0.18 g of a (3S,5S) form compound (Example 63B) of 3-(8H-indeno[1,2-d]thiazol-2-yl)-1-azabicyclo[3.3.0]octane was obtained from the fraction eluted with chloroform-methanol-aqueous ammonia (200:10:1).

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