Water → methyl 2-hydroxy-6,7-dihydro-5H-benzocycloheptene-8-carboxylate

Temperature

100 °C

To methyl 2-methoxy-6,7-dihydro-5H-benzocycloheptene-8-carboxylate (5.07 g, 21.8 mmol) dissolved in dichloromethane (100 ml) was added dropwise at −60° C. to −70° C. (inner temperature) boron tribromide (a 1 M solution in dichloromethane, 87 ml), and the resulting mixture was stirred for 5 hours while raising the temperature from −70° C. to room temperature. The reaction mixture was mixed with diethyl ether and water (100 ml) in the order, and was extracted with dichloromethane (100 ml, 50 ml×2). The combined organic layers were dried with anhydrous magnesium sulfate, and were then concentrated under reduced pressure. To the residue dissolved in methanol (150 ml) was added sulfuric acid (0.5 ml), and the resulting mixture was stirred under reflux with heating (100° C.) for 24 hours. The reaction mixture was concentrated under reduced pressure, was mixed with ethyl acetate (150 ml) and was washed with an aqueous saturated solution of sodium chloride (30 ml×3). After drying with anhydrous magnesium sulfate, the organic layer was concentrated under reduced pressure, diisopropyl ether was added to the residue and an insoluble material was collected by filtration. The insoluble material was washed with diisopropyl ether and was then dried under reduced pressure to obtain methyl 2-hydroxy-6,7-dihydro-5H-benzocycloheptene-8-carboxylate (4.31 g, 19.7 mmol, 90%).

1. temperaturewhile raising the temperature from −70° C. to room temperature
2. extractionwas extracted with dichloromethane (100 ml, 50 ml×2)
3. dry with materialThe combined organic layers were dried with anhydrous magnesium sulfate
4. concentrationwere then concentrated under reduced pressure
5. dissolutionTo the residue dissolved in methanol (150 ml)
6. additionwas added sulfuric acid (0.5 ml)
7. stirringthe resulting mixture was stirred
8. temperatureunder reflux
9. concentrationThe reaction mixture was concentrated under reduced pressure
10. additionwas mixed with ethyl acetate (150 ml)
11. washwas washed with an aqueous saturated solution of sodium chloride (30 ml×3)
12. dry with materialAfter drying with anhydrous magnesium sulfate
13. concentrationthe organic layer was concentrated under reduced pressure, diisopropyl ether
14. additionwas added to the residue
15. filtrationan insoluble material was collected by filtration
16. washThe insoluble material was washed with diisopropyl ether
17. customwas then dried under reduced pressure

ORD record

ord-354da3fae48a42319ec26e5e4fe5e96d

Source dataset

uspto-grants-2003_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06627651B1