反应详情

A suspension of 52 g (0.8 mole) of zinc powder and 800 mL of THF was cooled in an ice bath 44 mL (0.4 mole) of TiCl4 was added dropwise with stirring. The ice bath was removed and the reaction refluxed for 2 h. A solution of 26.45 g (0.094 mole) of N,N-diethyl-4-benzoylbenzamide and 23.9 g (0.094 mole) of 8-phenethyl-8-azabicyclo[3.2.1]octan-3-one, in 100 mL of THF was added dropwise and the reaction was refluxed 4 h. After cooling, the reaction mixture was poured into a beaker containing excess K2CO3 and ice. The mixture was extracted with ether, washed with brine, dried (K2CO3) and concentrated. There was obtained 47 g (˜0.1 mol) of crude (±)-N,N-diethyl-4-[(8-phenethyl-8-azabicyclo[3:2:1]oct-3-ylidene)phenylmethyl]benzamide as an oil. A sample of the oil and 38.33 g (0.1 mole) of (+)-ditoluoyl-D-tartaric acid were combined in 600 mL of acetonitrile. The solid was collected and recrystallized twice from acetonitrile. The solid was collected and partitioned between dilute sodium hydroxide and CH2Cl2. The organic solution was dried (K2CO3) and concentrated. The residue was converted to a hydrochloride salt (Et2O/HCl). It was recrystallized from 2-PrOH to give 5.6 g of white solid. Et2O, filtered, and precipitated after the addition of ethereal HCl; mp 210-211° C. MS m/z (MH+) 479. 1H NMR 300 MHz (CDCl3) δ 12.6 (s, 1H), 7.2-7.45 (m, 14H), 3.85 (S, 2H), 3.5-3.1 (m, 10H), 2.6 (d, 1H), 2.5 (d, 2H), 2.05 (m, 2H), 1.2 (br. s, 3H), 1.1 (br. s, 3H). [α]D25=−3.7°.

1. additionwas added dropwise
2. customThe ice bath was removed
3. temperaturethe reaction refluxed for 2 h
4. temperaturethe reaction was refluxed 4 h
5. temperatureAfter cooling
6. additionthe reaction mixture was poured into a beaker
7. extractionThe mixture was extracted with ether
8. washwashed with brine
9. dry with materialdried (K2CO3)
10. concentrationconcentrated