Water → HCID 18325103, compound

Butyl lithium (1.6M hexane solution: 36 ml) was added dropwise to a solution of helioalcohol (4.0 g) in benzene (100 ml) at room temperature. The mixture was stirred at room temperature for one hour, followed by addition of 4-methoxybenzonitrile (3.85 g) in benzene (20 ml). The mixture was stirred at room temperature overnight, followed by addition of water and extraction with ether. The organic layer was washed with water, dried over magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in toluene (75 ml), followed by addition of dimethyl fumarate (7.58 g) and trichloroacetic acid (0.3 g). The mixture was refluxed for 3 hours and concentrated under reduced pressure. The reside was dissolved in ethyl acetate and washed with water, an aqueous saturated sodium hydrogen carbonate solution and brine, dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified with silica gel column chromatography (silica gel: 50 g. eluent:ethyl acetate−hexane=1:2) to yield tetrahydro-2,4-epoxynaphthalene derivative (2.84 g) as a mixture of diastereoisomers. This was dissolved in a mixture of THF (5 ml) and methanol (5 ml), followed by addition of an aqueous NaOH (1.1 g) solution (5 ml). The mixture was stirred overnight and concentrated under reduced pressure. After being diluted with water, the mixture was washed with ethyl acetate. Conc. HCl was added to the aqueous layer until its pH becomes about 2.The mixture was extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in ether (50 ml), followed by addition of conc. HCl. The mixture was refluxed for 10 minutes and concentrated under reduced pressure, followed by addition of water. The resulting precipitate was collected by filtration and washed with methanol and ether to yield the title compound (2.64 g).

1. stirringThe mixture was stirred at room temperature overnight
2. washThe organic layer was washed with water
3. dry with materialdried over magnesium sulfate
4. concentrationconcentrated under reduced pressure
5. dissolutionThe residue was dissolved in toluene (75 ml)
6. additionfollowed by addition of dimethyl fumarate (7.58 g) and trichloroacetic acid (0.3 g)
7. temperatureThe mixture was refluxed for 3 hours
8. concentrationconcentrated under reduced pressure
9. dissolutionThe reside was dissolved in ethyl acetate
10. washwashed with water
11. dry with materialan aqueous saturated sodium hydrogen carbonate solution and brine, dried over magnesium sulfate
12. concentrationconcentrated under reduced pressure
13. customThe residue was purified with silica gel column chromatography (silica gel: 50 g. eluent:ethyl acetate−hexane=1:2)

ORD record

ord-41c8ea059a9140b6b9f66d8c3cc8d73e

Source dataset

uspto-grants-2002_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06340704B1