反应详情

温度

5 °C

To a well-stirred, nitrogen-blanketed suspension of lithium aluminum hydride (2.3 g, 60.0 mmol) in anhydrous tetrahydrofuran (150 mL), lactam IV (3.0 g, 11.5 mmol) was added in portions during 3-5 min at 25° C. Caution: and H2 evolution. This mixture was refluxed for 20 h then cooled to 0°-5° C. and the reaction quenched by the careful, sequential addition of water (2.5 mL), 1N NaOH (2.5 mL) and water 7.5 mL). This mixture was stirred at about 5° C. for 20 min then filtered through a pad of Celite. The collected aluminate salts were washed with tetrahydrofuran (200 mL) and the combined filtrate and wash was concentrated to dryness at reduced pressure, leaving 1.7 g of [3aR-[3aα,5α(2R*,3S*),6α,6aα]]-2-(Tetrahydro-6-hydroxy-2,2-dimethylfuro[2,3-d]-1,3-dioxol-5-yl)-3-pyrrolidinol (V) as a white powder. The collected aluminate salts were refluxed with 100 mL of tetrahydrofuran-water (9:1) for 45 min. The salts were filtered, washed with tetrahydrofuran (50 mL) and the combined filtrate evaporated to dryness, leaving 0.5 g more of V for a total yield of 77%. An analytical sample was obtained as fine, colorless needles by recrystallization from methanol mp 223°-225° C. (dec); [α]D25 =-5.0 (c 0.32, H2O); 1H NMR (CDCl3) δ 5.92 (d, 1, J=3.8 Hz, H-1), 4.55 (d, 1, J=3.8 Hz, H-2), 4.40 (ddd, J=5.3, 3.6, 1.6 Hz, H-6), 4.25 (d, 1, J=2.6 Hz, H-3), 4.13 (dd, 1, J=7.8, 2.6 Hz, H-4), 3.50 (m, 3, OH, NH), 3.18 (ddd, 1, J-11.2, 7.8, 7.6 Hz, H-8'), 3.12 (dd, 1, J=7.8, 3.6 Hz, H-5), 2.86 (ddd, 1, J=11.2, 9.5, 5.1 Hz, H-8), 2.05 (dddd, J=13.8, 9.5, 7.6, 5.3 Hz, H-7'), 1.86 (dddd, J=13.8, 7.8, 5.1, 1.6 Hz, H-7), 1.50 (s, 3, CH3), 1.32 (s, 3, CH3); 13C NMR δ 26.1, 26.6, 35.4, 43.2, 61.6, 70.6, 75.6, 77.9, 85.3, 103.8, 110.1; mass spectrum, m/z(rel intensity) 246 (MH+,100), 188 (MH+ -C3H6O, 52).

1. additionwas added in portions during 3-5 min at 25° C
2. temperatureThis mixture was refluxed for 20 h
3. temperaturethen cooled to 0°-5° C.
4. customthe reaction quenched by the careful,
5. additionsequential addition of water (2.5 mL), 1N NaOH (2.5 mL) and water 7.5 mL)
6. filtrationthen filtered through a pad of Celite
7. washThe collected aluminate salts were washed with tetrahydrofuran (200 mL)
8. washthe combined filtrate and wash
9. concentrationwas concentrated to dryness at reduced pressure