Sulfuric Acid → (3aR,4E,7aS)-4-(bromomethylene)-3a,4,5,6,7,7a-hexahydro-7a-methyl-3H-indene-1-carbaldehyde

Temperature

70 °C

The crude product of N-[(1Z)-{(E,3aS,7aR)-7-(bromomethylene)-octahydro-3a-methyl-2-oxoindene-3-ylidene}methyl]-N-phenethylacetamide (Compound 28) (178 mg, 0.428 mmol) was dissolved in methanol (2 ml), and sodium borohydride (20 mg, 0.529 mmol) was added thereto at 0° C. After stirring the resulting mixture for 10 minutes, the solvent was removed by evaporator. The residue was dissolved in ethyl acetate, and the resulting mixture was passed through a small amount of silica gel to obtain a crude product (154 mg). The obtained crude product (146 mg, 0.349 mmol) was dissolved in tetrahydrofuran (2 ml), and 2 N sulfuric acid (0.5 ml) was added thereto. The resulting mixture was heated to 70° C. and stirred for 4.5 hours. After cooling, the reaction solution was diluted with diethyl ether, and water was added thereto. The resulting mixture was extracted with diethyl ether. The combined organic layer was washed with saturated aqueous sodium hydrogen carbonate and with saturated brine, dried over magnesium sulfate, and evaporated under reduced pressure to obtain a crude product (140 mg). The crude product was purified by flash column chromatography to obtain (3aR,4E,7aS)-4-(bromomethylene)-3a,4,5,6,7,7a-hexahydro-7a-methyl-3H-indene-1-carbaldehyde (84 mg, 94%).

1. customat 0° C
2. customthe solvent was removed by evaporator
3. dissolutionThe residue was dissolved in ethyl acetate
4. customto obtain a crude product (154 mg)
5. customThe obtained crude product (146 mg, 0.349 mmol)
6. stirringstirred for 4.5 hours
7. temperatureAfter cooling
8. additionwas added
9. extractionThe resulting mixture was extracted with diethyl ether
10. washThe combined organic layer was washed with saturated aqueous sodium hydrogen carbonate and with saturated brine
11. dry with materialdried over magnesium sulfate
12. customevaporated under reduced pressure
13. customto obtain a crude product (140 mg)
14. customThe crude product was purified by flash column chromatography

ORD record

ord-972a536d15884efeb70600fb8d391c8d

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08173824B2