Dimethyl Sulfoxide → HCID 68618751, compound

Temperature

-78 °C

A tetrahydrofuran solution (120 mL) of (±)-(1′R,2′R,4′S,6′R)-spiro[1,3-dioxolan-2,7′-[3]oxatricyclo[4.2.0.02,4]octane] (J. Chem. Soc. Perkin Trans. 1, 1980, 852) (20.0 g, 119 mmol) was gradually added dropwise to a tetrahydrofuran suspension (480 mL) of lithium aluminum hydride (6.77 g, 178 mmol) with stirring at 0° C. The mixture was stirred overnight at room temperature, and tetrahydrofuran (200 mL), water (6.8 mL), a 15% aqueous sodium hydroxide solution (6.8 mL), and water (20.4 mL) were then added thereto while the reaction solution was cooled on ice. The mixture was stirred at room temperature for 3 hours. The mixture was filtered through Celite and concentrated under reduced pressure. Then, the obtained crude product was purified by silica gel column chromatography (separation from positional isomers in regard to hydroxyl groups) to obtain (±)-(1R,3R,5R)-spiro[bicyclo[3.2.0]heptane-6,2′-[1,3]dioxolan]-3-ol as an oil substance (7.78 g, 38%). Dimethyl sulfoxide (9.11 mL, 128 mmol) was added to a methylene chloride solution (110 mL) of oxalyl chloride (5.50 mL, 64.2 mmol) with stirring at −78° C., and the mixture was stirred at this temperature for 5 minutes. Then, a methylene chloride solution (30 mL) of the above-obtained alcohol (7.28 g, 42.8 mmol) was added thereto. The mixture was stirred at this temperature for 15 minutes. Then, triethylamine (23.7 mL, 171 mmol) was added thereto, and the mixture was heated to room temperature and stirred. The mixture was separated into aqueous and organic layers by the addition of 0.1 M hydrochloric acid. The organic layer was washed with 0.1 M hydrochloric acid, water, and saturated saline and then dried over anhydrous sodium sulfate. The residue was filtered and concentrated under reduced pressure. Then, the obtained crude product was purified by silica gel column chromatography to obtain the compound of interest as an oil substance (6.61 g, 92%).

1. stirringthe mixture was stirred at this temperature for 5 minutes
2. stirringThe mixture was stirred at this temperature for 15 minutes
3. temperaturethe mixture was heated to room temperature
4. stirringstirred
5. customThe mixture was separated into aqueous and organic layers
6. additionby the addition of 0.1 M hydrochloric acid
7. washThe organic layer was washed with 0.1 M hydrochloric acid, water, and saturated saline
8. dry with materialdried over anhydrous sodium sulfate
9. filtrationThe residue was filtered
10. concentrationconcentrated under reduced pressure
11. customThen, the obtained crude product
12. customwas purified by silica gel column chromatography
13. customto obtain the compound of interest as an oil substance (6.61 g, 92%)

ORD record

ord-3d643cd2f58942dd854938d446d3950b

Source dataset

uspto-grants-2011_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07947738B2