反应详情

温度

0 °C

Lithium triethylborohydride solution (4.24 L, 1.0M/THF) was steadily added (over 45 minutes) to a cold (−20° C.), stirred solution containing (±)-(4R*,5R*)-5-(Ethoxycarbonyl)-1-methyl-4-phenylpyrrolidin-2-one (500 g, 2.02 mole) in tetrahydrofuran (4L). The internal temperature was kept below −15° C. during the addition; the reaction was then allowed to warm to 0° C. and stirred for 1 hour. The reaction mixture was then cooled back down to −5° C. and cold 4N hydrochloric acid solution (made from 1000 mL ice water and 500 mL conc. HCl) was added over a 7-8 minute period with vigorous stirring. After stirring for 30 minutes (internal temp. ˜12° C.) the pH was adjusted to 7-8 by adding solid potassium carbonate. The reaction mixture was allowed to warm to room temperature, at which time the organic layer was separated and washed with brine (4 L). The organic layer was concentrated to near dryness, and hexane (200 ml) was added to precipitate a yellow solid. The solid was filtered, washed with hexane (500 ml) and dried under vacuum to give 345.12g (83%) of (±)-(4R*,5R*)-5-(hydroxymethyl)-1-methyl-4-phenylpyrrolidin-2-one. NMR (CDCl3) δ 2.35 (br s, 1H, OH), 2.56 (m, 1H, CH2), 2.94 (s, 3H, CH3), 3.01 (m, 1H, CH2), 3.34 (dd, J=13.5, 3.1 Hz, 1H, CH), 3.63 (dd, J=12.2, 3.4 Hz, 1H, CH), 3.75 (m, 2H, CH2), 7.31 (m, 5H, Ar).

1. additionThe internal temperature was kept below −15° C. during the addition
2. stirringstirred for 1 hour
3. additionwas added over a 7-8 minute period with vigorous stirring
4. stirringAfter stirring for 30 minutes (internal temp. ˜12° C.) the pH
5. temperatureto warm to room temperature, at which time the organic layer
6. customwas separated
7. washwashed with brine (4 L)
8. concentrationThe organic layer was concentrated
9. additionwas added
10. customto precipitate a yellow solid
11. filtrationThe solid was filtered
12. washwashed with hexane (500 ml)
13. customdried under vacuum