反应详情

温度

-40 °C

3-Benzyl-5,6,7,8,9,10-hexahydro[1,2,4]triazolo[4,3-a]azocine (287.6 mg) and 1-bromo-3-chloro-2-methylpropane (140 μL) were dissolved in anhydrous, deoxygenated tetrahydrofuran, and the solution was cooled to −40° C. under an argon atmosphere. Potassium bis(trimethylsilyl)amide (KHMDS, 0.5M in toluene, 2.5 mL) was added dropwise. After 30 minutes, a second aliquot of KHMDS (2.5 mL) was added. After 30 additional minutes, KHMDS (2.15 mL) was added again, and the solution was allowed to slowly warm to room temperature. After one hour, the reaction was quenched with water and added to brine. After extraction with ethyl acetate, the organic layer was dried with magnesium sulfate, filtered, evaporated and purified by silica gel chromatography to give 3-[1-(4-chlorophenyl)-(Z)-3-(methoxymethoxy)cyclobutyl]-5,6,7,8,9,10-hexahydro[1,2,4]triazolo[4,3-a]azocine (4-10) as a ca. 1.2:1 mixture of isomers.

1. customdeoxygenated tetrahydrofuran
2. additionPotassium bis(trimethylsilyl)amide (KHMDS, 0.5M in toluene, 2.5 mL) was added dropwise
3. additiona second aliquot of KHMDS (2.5 mL) was added
4. additionAfter 30 additional minutes, KHMDS (2.15 mL) was added again
5. temperatureto slowly warm to room temperature
6. waitAfter one hour
7. customthe reaction was quenched with water
8. additionadded to brine
9. extractionAfter extraction with ethyl acetate
10. dry with materialthe organic layer was dried with magnesium sulfate
11. filtrationfiltered
12. customevaporated
13. custompurified by silica gel chromatography