反应详情

To a solution of 3-[(3,6-dihydro-4-phenyl-1(2H)-pyridinyl)methyl]cyclohexanone (Example A) (5.9 g) in 400 mL of tetrahydrofuran is added a solution of phenylmagnesium bromide (9.13 mL, 3.0M in diethyl ether), dropwise under nitrogen, at 0° C. The mixture is stirred at room temperature for 1 hour, then cooled in an ice bath and quenched with 250 mL of 10% aqueous hydrochloric acid solution. The solvent is evaporated in vacuo and the residue partitioned into chloroform/5% aqueous ammonium hydroxide solution. The organic extract is dried over magnesium sulfate and filtered. The filtrate is treated with trifluoroacetic acid (4.2 mL) and stirred overnight at room temperature. The solvent is evaporated in vacuo, and the residue is partitioned into ethyl acetate/5% aqueous ammonium hydroxide solution. The organic extract is dried over magnesium sulfate, filtered, and concentrated. The crude product is purified by medium pressure chromatography to give 3.9 g of (±) -1,2,3,6-tetrahydro-4-phenyl-1-[(3-phenyl-3-cyclohexen-1-yl)methyl]pyridine; mp 90°-95° C. as an off-white solid (Example 1) and 2.7 g of (±)-1,2,3,6-tetrahydro-4-phenyl-1-[(3-phenyl-2-cyclohexen-1-yl)methyl]pyridine; mp 124°-126° C. as a tan solid (Example 1a).

1. customat 0° C
2. temperaturecooled in an ice bath
3. customquenched with 250 mL of 10% aqueous hydrochloric acid solution
4. customThe solvent is evaporated in vacuo
5. customthe residue partitioned into chloroform/5% aqueous ammonium hydroxide solution
6. extractionThe organic extract
7. dry with materialis dried over magnesium sulfate
8. filtrationfiltered
9. additionThe filtrate is treated with trifluoroacetic acid (4.2 mL)
10. stirringstirred overnight at room temperature
11. customThe solvent is evaporated in vacuo
12. customthe residue is partitioned into ethyl acetate/5% aqueous ammonium hydroxide solution
13. extractionThe organic extract
14. dry with materialis dried over magnesium sulfate
15. filtrationfiltered
16. concentrationconcentrated
17. customThe crude product is purified by medium pressure chromatography