反应详情

A 3 L three-necked round-bottomed flask was equipped with mechanical stirrer, thermometer and adapter, additional funnel, and nitrogen inlet (on top of addition funnel, positive pressure through a bubbler). With a rapid stream of nitrogen going through the bubbler, the stopper was removed and the flask was charged with KHMDS (415.8 g, 2.08 mol) and then anhydrous THF (1 L). To the stirred and cooled (ice/methanol bath, internal temperature of solution was −8° C.) KHMDS/THF solution was added dropwise a solution of MeCN (70 g) in THF (110 mL) over a period of 22 min followed immediately by the relatively rapid (4 min) addition of a solution of 5 (79.06 g, 0.262 mol) in THF (400 mL), after which time the internal temperature of the reaction mixture had reached 10° C. With continued cooling (1 h) the internal temperature was −6° C. and by TLC the reaction appeared complete. After an additional 30 min (internal temperature of −3° C.), the reaction mixture was quenched with saturated brine (1 L) and diluted with EtOAc (500 mL). After removing the aqueous layer, the organic solution was dried (Na2SO4), filtered, and evaporated to dryness (to an oil) followed by completely dissolving in IPA (150 mL), diluting with heptane (300 mL), adding seed crystals (prepared by dissolving ˜100 mg of crude oil in IPA (˜150 mg) and diluting with heptane (˜2.5 mL)), and allowing to stand overnight. After stirring to break up the crystalline solid, the solid was filtered, washed with 250 mL 2:1 heptane/IPA and then multiple washes with heptane and air dried to give 64.38 g (yield of 76%) of title product 6 as a crystalline tan solid (LC purity of 99.3%). Another 5.88 g of less pure material was obtained from the filtrate.

1. customA 3 L three-necked round-bottomed flask was equipped with mechanical stirrer
2. additionthermometer and adapter, additional funnel, and nitrogen inlet (on top of addition funnel
3. customWith a rapid stream of nitrogen going through the bubbler, the stopper was removed
4. customhad reached 10° C
5. temperatureWith continued cooling (1 h) the internal temperature
6. customwas −6° C. and by TLC
7. customthe reaction mixture was quenched with saturated brine (1 L)
8. additiondiluted with EtOAc (500 mL)
9. customAfter removing the aqueous layer
10. dry with materialthe organic solution was dried (Na2SO4)
11. filtrationfiltered
12. customevaporated to dryness (to an oil)
13. dissolutionby completely dissolving in IPA (150 mL)
14. additiondiluting with heptane (300 mL)
15. additionadding
16. customseed crystals (prepared by dissolving ˜100 mg of crude oil in IPA (˜150 mg) and diluting with heptane (˜2.5 mL))
17. waitto stand overnight
18. stirringAfter stirring
19. filtrationthe solid was filtered
20. washwashed with 250 mL 2:1 heptane/IPA
21. dry with materialmultiple washes with heptane and air dried