Triethylamine → methyl 2-methoxy-6,7-dihydro-5H-benzocycloheptene-8-carboxylate

Temperature

-40 °C

To methyl 3-methoxy-5-oxo-6,7,8,9-tetrahydro-5H-benzocycloheptene-6-carboxylate (1079 mg, 4.35 mmol) dissolved in a mixed solvent of dichloromethane (10 ml) and methanol (2.5 ml) was added at −40° C. (inner temperature) sodium borohydride (300 mg, 7.93 mmol), and the resulting mixture was stirred at −15° C. to −10° C. for 1.5 hours. The reaction mixture was cooled to −40° C., was mixed with water (10 ml) and extracted with dichloromethane (×3). The combined organic layers were dried with anhydrous magnesium sulfate and were then concentrated under reduced pressure. To the residue dissolved in dichloromethane (15 ml) were added at 0° C. triethylamine (3.03 ml, 21.7 mmol) and methanesulfonyl chloride (0.505 ml, 6.52 mmol), and the resulting mixture was stirred at room temperature for 18 hours. In order to complete the reaction, DBU (1.95 ml, 13.0 mmol) was added, and the resulting mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure, was mixed with water and was extracted with ethyl acetate (×3). The combined organic layers were washed with 1 N hydrochloric acid (×3) and an aqueous saturated solution of sodium chloride, were dried with anhydrous magnesium sulfate and were then concentrated under reduced pressure, and the residue was subjected to column chromatography (silica gel, ethyl acetate/hexane=1/9). The objective fractions were concentrated under reduced pressure to obtain methyl 2-methoxy-6,7-dihydro-5H-benzocycloheptene-8-carboxylate (730 mg, 3.14 mmol, 72%).

1. extractionextracted with dichloromethane (×3)
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 (15 ml)
5. stirringthe resulting mixture was stirred at room temperature for 18 hours
6. additionwas added
7. stirringthe resulting mixture was stirred at room temperature for 3 hours
8. concentrationThe reaction mixture was concentrated under reduced pressure
9. additionwas mixed with water
10. extractionwas extracted with ethyl acetate (×3)
11. washThe combined organic layers were washed with 1 N hydrochloric acid (×3)
12. dry with materialan aqueous saturated solution of sodium chloride, were dried with anhydrous magnesium sulfate
13. concentrationwere then concentrated under reduced pressure
14. concentrationThe objective fractions were concentrated under reduced pressure

ORD record

ord-ffdef57bbb0d490bae97a5ad400d9cef

Source dataset

uspto-grants-2003_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06627651B1