반응 #2635

반응 방정식

tert-butyl methyl ether

lithium aluminum hydride

4-tert-butyldimethylsiloxy-2-cyclopentenone

lithium iodide

→

title compound

수율 74.0%

cis-4-tert-butyldimethylsilyloxy-2-cyclopentenol

수율 74.0%

용매

toluene

heptane

반응 조건

후처리

1. 1
   기타the temperature of the reaction at or
2. 2
   workup.ADDITIONbelow -15° C. (total addition time is approximately 3 minutes)
3. 3
   workup.STIRRINGThe reaction is stirred for one hour at -20° C.
4. 4
   기타it is quenched by slow addition of aqueous sodium hydroxide (1N, 250 mL) at a rate
5. 5
   기타the temperature of the reaction below 20° C
6. 6
   여과The resulting suspension is then filtered through a pad of diatomaceous earth
7. 7
   세척the pad is subsequently rinsed with toluene (400 mL)
8. 8
   기타The filtrate phases are separated
9. 9
   추출the aqueous phase is extracted with toluene (300 mL)
10. 10
    추출The organic phase and organic extract
11. 11
    세척rinsed with aqueous sodium hydroxide (1N, 300 mL), brine (300 mL)
12. 12
    건조dried over anhydrous magnesium sulfate
13. 13
    여과filtered
14. 14
    농축concentrated under vacuum (40° C., 20 mmHg)
15. 15
    workup.DISTILLATIONThe residue is then purified by Kugelrohr distillation (60°-80° C., 1 mmHg)

실험 절차

A mechanically stirred solution of 4-tert-butyldimethylsiloxy-2-cyclopentenone (50.2 g, 236 mmol) in anhydrous toluene (1L) under an atmosphere of argon is treated with lithium iodide (160 g, 1.20 mol). The mixture is cooled to -20° C. and treated with lithium aluminum hydride (9.0 g, 237 mmol) in one portion. The reaction is then stirred for 5 minutes and anhydrous tert-butyl methyl ether (200 mL) is added at a rate that maintains the temperature of the reaction at or below -15° C. (total addition time is approximately 3 minutes). The reaction is stirred for one hour at -20° C. and then it is quenched by slow addition of aqueous sodium hydroxide (1N, 250 mL) at a rate that maintains the temperature of the reaction below 20° C. The resulting suspension is then filtered through a pad of diatomaceous earth and the pad is subsequently rinsed with toluene (400 mL). The filtrate phases are separated and the aqueous phase is extracted with toluene (300 mL). The organic phase and organic extract are combined, rinsed with aqueous sodium hydroxide (1N, 300 mL), brine (300 mL), dried over anhydrous magnesium sulfate, filtered and concentrated under vacuum (40° C., 20 mmHg). The residue is then purified by Kugelrohr distillation (60°-80° C., 1 mmHg) to provide the title compound (37.4 g, 74% yield) as a colorless oil; cis/trans/1-2+1-4 addition, 95.3/2.1/2.6; Rf =0.20, 20% ethyl acetate/hexane, GC retention time for the title compound is 13.95 minutes, while GC retention times for the byproducts corresponding to compounds 3 (trans) and 4 (1-2+1-4 addition) in Scheme I wherein Pg is a TBDMS group are 14.45 min. and 14.06 min. respectively; for the title compound, 1H NMR (CDCl3)δ 5.93 (dt, J=5.5, 1.7 Hz, 1H), 5.84 (dr, J=5.5, 1.6 Hz, 1H), 4.63-4.68 (m, 1H), 4.52-4.62 (m, 1H), 2.76-2.86 (bs, 1H), 2.69 (dr, J=13.8, 7.1 Hz, 1H), 1.52 (dt, J=13.8, 4.7 Hz, 1H), 0.90 (s, 9H), 0.09 (s, 6H); 13C NMR (CDCl3) δ 136.7, 135.6, 75.1, 75.0, 44.5, 25.9, 18.1; IR (neat) νmax 3373, 2957, 2932 cm-1 ; MS (EI) m/e (% relative intensity) 157 (M+ -57).

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