反应详情

A solution of 1-(1,4-dioxaspiro[4,5]dec-8-ylacetyl)-4-(2-pyridinyl)piperazine (17.0 g) in 500 mL of dry tetrahydrofuran is treated with sodium borohydride (6.81 g) under nitrogen and the resulting suspension is treated dropwise with a solution of boron trifluoride etherate (29.5 mL) in 100 mL of tetrahydrofuran. The reaction mixture is stirred at room temperature overnight. A solution of glacial acetic acid (10.3 mL) in 100 mL of tetrahydrofuran is added dropwise, and the mixture stirred at room temperature for 2 hours. The solvent is evaporated in vacuo and the residue refluxed with 250 mL of a 10% solution of hydrochloric acid and 250 mL of acetone for 2 hours. The mixture is concentrated in vacuo to about one-half of the original volume. The remaining aqueous solution is washed twice with ethyl acetate and made basic with ammonium hydroxide. The crude product is extracted into ethyl acetate (2×300 mL). the organic extract is dried over magnesium sulfate and concentrated in vacuo. The reaction mixture is purified by MPLC (silica; 2% methanol, 98% chloroform) to give 9.73 g of the title compound as a colorless solid; mp 104°-106° C.

1. stirringthe mixture stirred at room temperature for 2 hours
2. customThe solvent is evaporated in vacuo
3. temperaturethe residue refluxed with 250 mL of a 10% solution of hydrochloric acid and 250 mL of acetone for 2 hours
4. concentrationThe mixture is concentrated in vacuo to about one-half of the original volume
5. washThe remaining aqueous solution is washed twice with ethyl acetate
6. extractionThe crude product is extracted into ethyl acetate (2×300 mL)
7. extractionthe organic extract
8. dry with materialis dried over magnesium sulfate
9. concentrationconcentrated in vacuo
10. customThe reaction mixture is purified by MPLC (silica; 2% methanol, 98% chloroform)