Ammonium Chloride → HCID 57827350, compound

Temperature

-78 °C

THF (3 mL) and toluene (20 mL) were added to 2-bromofluorobenzene (1.23 mL, specific gravity: 1.614 g/cm3) under a nitrogen atmosphere, and the mixture was cooled to −78° C. A solution of n-butyllithium in hexane (3.9 mL, 2.63 M) was slowly added so that the internal temperature was maintained at −60° C. or less. After completion of the addition, the mixture was stirred for 10 minutes. After slowly adding a boron trifluoride-diethyl ether complex (1.29 mL), a solution of (±)-(3aR*,6S*)-6-methoxy-3,3a,4,5,6,7-hexahydrobenz[c]isoxazole obtained in Preparation Example 57-(4) (796 mg) in toluene (10 mL) was slowly added so that the internal temperature was maintained at −60° C. or less. After completion of the addition, the mixture was stirred for one hour and 50 minutes. A saturated ammonium chloride solution was added, followed by warming to room temperature. Ethyl acetate and water were added, followed by further stirring. The aqueous layer was separated and then the organic layer was sequentially washed with a saturated ammonium chloride solution, water and brine. The resulting organic layer was dried over anhydrous magnesium sulfate. The drying agent was removed by filtration and then the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound (711 mg).

1. temperaturewas maintained at −60° C. or less
2. additionAfter completion of the addition
3. additionAfter slowly adding a boron trifluoride-diethyl ether complex (1.29 mL)
4. additionwas slowly added so that the internal temperature
5. temperaturewas maintained at −60° C. or less
6. additionAfter completion of the addition
7. stirringthe mixture was stirred for one hour and 50 minutes
8. temperatureby warming to room temperature
9. customThe aqueous layer was separated
10. washthe organic layer was sequentially washed with a saturated ammonium chloride solution, water and brine
11. dry with materialThe resulting organic layer was dried over anhydrous magnesium sulfate
12. customThe drying agent was removed by filtration
13. concentrationthe filtrate was concentrated under reduced pressure
14. customThe resulting residue was purified by silica gel column chromatography

ORD record

ord-74a7a78dbbb1461382f11b094eecd01c

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08946211B2