Ethylene Oxide → HCID 18381564, compound

Temperature

-78 °C

A solution of 5-bromo-2-chloro-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide (3.0 g, Example 23a) in anhydrous tetrahydrofuran (100 ml) was cooled to −78° C. under a nitrogen atmosphere. A solution of methyllithium (1.4M in diethyl ether, 4.9 ml) was added over 2 min. The mixture was stirred at −78° C. for 10 min., then a solution tert-butyllithium (1.7M in pentane, 9.3 ml) was added dropwise. The mixture was stirred at −78° C. for a further 10 min., then ethylene oxide (1.0 ml) was added. The resulting solution was stirred at −78° C. for 30 min. then was warmed to 0° C. and stirred for another 6 h. The reaction mixture was quenched with saturated aqueous ammonium chloride solution (70 ml) and extracted with ethyl acetate (3×100 ml). The combined extracts were dried over anhydrous magnesium sulfate, filtered, and the filtrate concentrated under reduced pressure. The residue was purified by chromatography over silica gel eluting with dichloromethane:ethanol (98:2) to give the subtitle compound as a pale yellow solid (0.89 g).

1. stirringThe mixture was stirred at −78° C. for a further 10 min.
2. stirringThe resulting solution was stirred at −78° C. for 30 min.
3. temperaturethen was warmed to 0° C.
4. stirringstirred for another 6 h
5. customThe reaction mixture was quenched with saturated aqueous ammonium chloride solution (70 ml)
6. extractionextracted with ethyl acetate (3×100 ml)
7. dry with materialThe combined extracts were dried over anhydrous magnesium sulfate
8. filtrationfiltered
9. concentrationthe filtrate concentrated under reduced pressure
10. customThe residue was purified by chromatography over silica gel eluting with dichloromethane:ethanol (98:2)

ORD record

ord-de55d5abeb144a218d487f1455810579

Source dataset

uspto-grants-2002_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06492355B1