Triethylamine → methyl 2-(4-phenylbenzyloxy)-6,7-dihydro-5H-benzocycloheptene-8-carboxylate

Temperature

-40 °C

To methyl 3-(4-phenylbenzyloxy)-5-oxo-6,7,8,9-tetrahydro-5H-benzocycloheptene-6-carboxylate (2.31 g, 5.77 mmol) dissolved in a mixed solvent of dichloromethane (50 ml) and methanol (15 ml) was added at −40° C. (inner temperature) sodium borohydride (327 mg, 8.64 mmol), and the resulting mixture was stirred at −20° C. to −10° C. for 2 hours. The reaction mixture was cooled to −40° C., was mixed with water (20 ml) and extracted with dichloromethane (50 ml, 10 ml×2). The combined organic layers were dried with anhydrous magnesium sulfate and were then concentrated under reduced pressure. To the residue dissolved in dichloromethane (40 ml) were added at 0° C. triethylamine (4.02 ml, 28.8 mmol) and methanesulfonyl chloride (0.67 ml, 8.7 mmol), and the resulting mixture was stirred at room temperature for 16 hours. In order to complete the reaction, DBU (2.59 ml, 17.3 mmol) was added, and the resulting mixture was stirred at room temperature for 12 hours. The reaction mixture was concentrated under reduced pressure, was mixed with water (30 ml) and was extracted with ethyl acetate (40 ml, 15 ml×2). The combined organic layers were washed with 1 N hydrochloric acid (5 ml×3), were dried with anhydrous magnesium sulfate and were then concentrated under reduced pressure, and the residue was subjected to column chromatography (silica gel: 60 g, toluene). The objective fractions were concentrated under reduced pressure and the residue was mixed with ethyl acetate and diisopropyl ether, 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-(4-phenylbenzyloxy)-6,7-dihydro-5H-benzocycloheptene-8-carboxylate (1.31 g, 3.41 mmol, 59%).

1. extractionextracted with dichloromethane (50 ml, 10 ml×2)
2. dry with materialThe combined organic layers were dried with anhydrous magnesium sulfate
3. concentrationwere then concentrated under reduced pressure
4. dissolutionTo the residue dissolved in dichloromethane (40 ml)
5. stirringthe resulting mixture was stirred at room temperature for 16 hours
6. additionwas added
7. stirringthe resulting mixture was stirred at room temperature for 12 hours
8. concentrationThe reaction mixture was concentrated under reduced pressure
9. additionwas mixed with water (30 ml)
10. extractionwas extracted with ethyl acetate (40 ml, 15 ml×2)
11. washThe combined organic layers were washed with 1 N hydrochloric acid (5 ml×3)
12. dry with materialwere dried with anhydrous magnesium sulfate
13. concentrationwere then concentrated under reduced pressure
14. concentrationThe objective fractions were concentrated under reduced pressure
15. additionthe residue was mixed with ethyl acetate and diisopropyl ether
16. filtrationan insoluble material was collected by filtration
17. washThe insoluble material was washed with diisopropyl ether
18. customwas then dried under reduced pressure

ORD record

ord-66eb600b7741478ab15ad589953435f4

Source dataset

uspto-grants-2003_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06627651B1