反应详情

Titanium trichloride, 10.1 g (65.6 mmol), was weighed into a round-bottomed flask in a glove bag under an argon atmosphere. Freshly distilled tetrahydrofuran (from LAH), 70 mL, was added quickly under argon flow. (Care should be taken, as this addition can be exothermic.) The purple suspension was stirred vigorously so as to break up the solid material adhering to the walls of the flask. After 15 minutes, zinc dust, 7.1 g, was added all at once under argon with continued stirring. A moderate exotherm resulted in a reddish-brown mixture which did not contain black suspended solids. After 20 minutes stirring, the mixture was cooled in an ice bath and several drops of triethylamine were added with exclusion of air. After an exotherm, an additional 12 ml N(Et)3 was added. The mixture was then refluxed for 2 hours. A solution of 5-chloro-2-adamantanone, 3.7 g (20 mmol), and 2,2,2-trifluoroethyl 4-chloro-3-methoxybenzoate, 2.6 g (10 mmol) in dry THF, 40 mL, was added dropwise to the refluxing brown mixture over approximately 35 minutes. Reflux was continued for 2.5 hours whereupon TLC showed unreacted ester starting material. An additional 1.10 g of the chloro-adamantanone was added as a solid under argon flow. After another 2.5 hours of reflux, the cooled reaction mixture was stirred overnight at room temperature. The solvents were rotary evaporated from the cooled reaction mixture to yield a brown-black gum. This gum was triturated with hexanes, 100 mL, and ethyl acetate, 20 mL. The yellow-orange supernate was decanted and the trituration procedure was repeated. After 10 minutes of agitation, triethylamine and methanol, 2 mL each, were added. The gum began to stiffen and eventually became a lumpy solid. The solid was broken up and the supernate decanted. One final trituration was accomplished with 5% ethyl acetate-hexanes. The combined decanted supernates were rotary evaporated to a light yellow oil. The residue obtained after rotary evaporation of the filtrate was applied to a 2.1×20 cm. column of silica gel. The column was eluted with 5 to 10% ethyl acetate in hexanes to five fractions which contained a mid Rf UV-active spot, contaminated by iodine-sensitive spots both above and below. These fractions were rotary evaporated to give 2.52 g of a semisolid paste. An I.R. spectrum showed absorptions at 1583 and 1567 cm-1. The impure product as used directly in the next reaction step.

1. addition(Care should be taken, as this addition
2. customA moderate exotherm resulted in a reddish-brown mixture which
3. stirringAfter 20 minutes stirring
4. temperaturethe mixture was cooled in an ice bath
5. temperatureThe mixture was then refluxed for 2 hours
6. temperatureReflux
7. waitwas continued for 2.5 hours whereupon TLC
8. temperatureAfter another 2.5 hours of reflux
9. customthe cooled reaction mixture
10. stirringwas stirred overnight at room temperature
11. customThe solvents were rotary evaporated from the cooled reaction mixture
12. customto yield a brown-black gum
13. customThis gum was triturated with hexanes, 100 mL, and ethyl acetate, 20 mL
14. customThe yellow-orange supernate was decanted
15. waitAfter 10 minutes of agitation, triethylamine and methanol, 2 mL each
16. additionwere added
17. customThe combined decanted supernates
18. customwere rotary evaporated to a light yellow oil
19. customThe residue obtained
20. customafter rotary evaporation of the filtrate
21. washThe column was eluted with 5 to 10% ethyl acetate in hexanes to five fractions which
22. customThese fractions were rotary evaporated