tert-Butyl methyl ether → 2-Cyclopenten-1-ol, 4-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-, cis-

온도

-20 °C

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).

1. customthe temperature of the reaction at or
2. additionbelow -15° C. (total addition time is approximately 3 minutes)
3. stirringThe reaction is stirred for one hour at -20° C.
4. customit is quenched by slow addition of aqueous sodium hydroxide (1N, 250 mL) at a rate
5. customthe temperature of the reaction below 20° C
6. filtrationThe resulting suspension is then filtered through a pad of diatomaceous earth
7. washthe pad is subsequently rinsed with toluene (400 mL)
8. customThe filtrate phases are separated
9. extractionthe aqueous phase is extracted with toluene (300 mL)
10. extractionThe organic phase and organic extract
11. washrinsed with aqueous sodium hydroxide (1N, 300 mL), brine (300 mL)
12. dry with materialdried over anhydrous magnesium sulfate
13. filtrationfiltered
14. concentrationconcentrated under vacuum (40° C., 20 mmHg)
15. distillationThe residue is then purified by Kugelrohr distillation (60°-80° C., 1 mmHg)

ORD 기록

ord-a6ecf5a0a0dd4c20a3f46740fd5078c7

출처 데이터셋

uspto-grants-1998_03

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US05728899