Water → HCID 584218, compound

Temperature

50 °C

1 mL of 1 M tetrabutylammonium fluoride-tetrahydrofuran solution was added to the compound obtained in the above 1, and stirred at 50° C. for 4 hours. Then, the reaction liquid was cooled to room temperature. Water was added to the reaction liquid, and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated saline water, and dried with anhydrous sodium sulfate. The solvent was evaporated off under reduced pressure, and the residue was separated and purified through basic silica gel column chromatography (hexane/ethyl acetate=9/1 to 4/1) to obtain 19 mg of a racemate of the entitled compounds. The racemate was optically resolved in an optically-active column (Daicel's CHRALPAC AD column, 2 cm×25 cm; 0.1% diethylamine, hexane/isopropyl alcohol=9/1; flow rate, 20 mL/min). From the former fraction (retention time; 8.1 min), 6.4 mg of (7S,9R)-7-(spiro[8-aza-bicyclo[3.2.1]octa-3,1′(3′H)-isobenzofuran]-8-ylmethyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-ol was obtained; and from the latter fraction (retention time; 9.8 min), 6.4 mg of the (7R,9S) form was obtained, both as a white powder.

1. customobtained in the above 1
2. customThen, the reaction liquid
3. temperaturewas cooled to room temperature
4. extractionextracted with ethyl acetate
5. washThe ethyl acetate layer was washed with saturated saline water
6. dry with materialdried with anhydrous sodium sulfate
7. customThe solvent was evaporated off under reduced pressure
8. customthe residue was separated
9. custompurified through basic silica gel column chromatography (hexane/ethyl acetate=9/1 to 4/1)
10. customto obtain 19 mg of a racemate of the entitled compounds

ORD record

ord-4cf006341b0844cb9c465718d5e68c43

Source dataset

uspto-grants-2010_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07855294B2