Reaktion #155620

Reaktionsgleichung

Sodium hydride

(2S)-6-(tetrahydro-2H-pyran-2-yloxy)hex-4-yn-2-ol

1,1-diethoxy-2-iodoethane

1,1-diethoxy-2-iodoethane

→

product

2-{[(5S)-5-(2,2-diethoxyethoxy)hex-2-yn-1-yl]oxy}tetrahydro-2H-pyran

Lösungsmittel

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeremained below 5° C
2. 2
   Sonstigethe cooling bath was removed
3. 3
   Temperaturwas again cooled to 0° C
4. 4
   Temperaturat a rate that maintained the reaction temperature below 10° C
5. 5
   SonstigeAfter removal of the cooling bath
6. 6
   workup.STIRRINGthe reaction mixture was stirred at room temperature for 30 minutes
7. 7
   Sonstigeplaced in a 50° C.
8. 8
   Sonstigefor 90 minutes
9. 9
   TemperaturHeating
10. 10
    workup.WAITwas continued for 1 hour, at which time
11. 11
    Temperaturthe reaction mixture was cooled in an ice bath
12. 12
    Sonstigequenched with a mixture of saturated aqueous ammonium chloride solution (210 mL) and saturated aqueous sodium chloride solution (210 mL)
13. 13
    ExtraktionThe resulting mixture was extracted with tert-butyl methyl ether (3×200 mL)
14. 14
    Waschenthe combined organic layers were washed with saturated aqueous sodium chloride solution
15. 15
    Trocknendried over sodium sulfate
16. 16
    Filtrationfiltered
17. 17
    Einengenconcentrated in vacuo

Vorschrift

Sodium hydride (60% in mineral oil, 9.8 g, 240 mmol) was added portion-wise to a 0° C. solution of (2S)-6-(tetrahydro-2H-pyran-2-yloxy)hex-4-yn-2-ol (synthesized as described by G. V. M. Sharma and K. Veera Babu, Tetrahedron: Asymmetry 2007, 18, 2175-2184) (27.0 g, 136 mmol) in tetrahydrofuran (130 mL), at a rate such that the reaction temperature remained below 5° C. After 5 minutes, the cooling bath was removed and the reaction mixture was allowed to stir at room temperature for 3.5 hours, whereupon it was again cooled to 0° C. A solution of 1,1-diethoxy-2-iodoethane (49.9 g, 204 mmol) in tetrahydrofuran (5 mL) was added drop-wise over 30 minutes, at a rate that maintained the reaction temperature below 10° C. After removal of the cooling bath, the reaction mixture was stirred at room temperature for 30 minutes, and then placed in a 50° C. oil bath for 90 minutes, at which time additional 1,1-diethoxy-2-iodoethane (3.3 g, 14 mmol) was added, as a solution in tetrahydrofuran (5 mL). Heating was continued for 1 hour, at which time the reaction mixture was cooled in an ice bath and quenched with a mixture of saturated aqueous ammonium chloride solution (210 mL) and saturated aqueous sodium chloride solution (210 mL). The resulting mixture was extracted with tert-butyl methyl ether (3×200 mL), and the combined organic layers were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated in vacuo. Silica gel chromatography (Gradient: 0% to 50% ethyl acetate in hexanes) afforded the product as a yellow oil. Yield: 22.8 g, 72.5 mmol, 53%. 1H NMR (500 MHz, CDCl3), characteristic peaks: δ 4.80 (t, J=3.5 Hz, 1H), 4.59 (t, J=5.2 Hz, 1H), 4.28 (dt, half of ABX2 pattern, J=15.3, 2.1 Hz, 1H), 4.20 (dt, half of ABX2 pattern, J=15.3, 2.1 Hz, 1H), 3.81-3.87 (m, 1H), 2.48-2.56 (m, 1H), 2.28-2.36 (m, 1H), 1.78-1.88 (m, 1H), 1.69-1.77 (m, 1H), 1.25 (d, J=6.1 Hz, 3H), 1.22 (t, J=7.1 Hz, 6H).

Quelle