Reaktion #480752

Reaktionsgleichung

N-benzyl diol

N-Fmoc glycinal

tetrahydrofuran

sodium hydride

N-tosylimidazole

→

N-benzyl morpholine

Ausbeute 63.0%

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigebefore removing the cooling bath
2. 2
   workup.WAITAfter 1 hr at 23° C.
3. 3
   Sonstigewas returned to a 0° C.
4. 4
   Sonstigefor 10 min
5. 5
   workup.ADDITIONwas observed subsequent to the addition of each portion)
6. 6
   workup.STIRRINGAfter stirring
7. 7
   Sonstigethe resulting reaction solution for a further 10 min at 0° C.
8. 8
   Sonstigethe cooling bath was again removed
9. 9
   workup.WAITAfter 1 hr at 23° C.
10. 10
    Sonstigeexcess sodium hydride was CAREFULLY quenched by the slow addition of 30 mL saturated aqueous ammonium chloride to the reaction suspension at 0° C
11. 11
    SonstigeThe reaction mixture was then partitioned between 340 mL ammounium chloride (sat., aq.) and 370 mL diethyl ether
12. 12
    Sonstigethe organic layer separated
13. 13
    Waschenwashed further with 1×300 mL water and 1×200 mL brine
14. 14
    Extraktionextracted with 2×200 mL diethyl ether
15. 15
    Trocknendried over sodium sulfate
16. 16
    SonstigeConcentration of the extracts in vacuo provided a yellow oil, which
17. 17
    Sonstigewas purified by flash column chromatography (SiO2, 20% ethyl acetate-hexanes)

Vorschrift

A solution of N-benzyl diol 4 (1.54 g, 4.02 mmol, 1.0 equiv) in 40.0 mL tetrahydrofuran was stirred at 0° C. for 10 min and was then added via cannula to sodium hydride (254.2 mg, 10.06 mmol, 2.5 equiv). The resulting white suspension was stirred vigorously at 0° C. for 5 min before removing the cooling bath. After 1 hr at 23° C., the reaction suspension was returned to a 0° C. bath for 10 min and N-tosylimidazole (894.5 mg, 4.02 mmol. 1.0 equiv) added in 3 portions over 12 min (gas evolution was observed subsequent to the addition of each portion). After stirring the resulting reaction solution for a further 10 min at 0° C., the cooling bath was again removed. After 1 hr at 23° C., excess sodium hydride was CAREFULLY quenched by the slow addition of 30 mL saturated aqueous ammonium chloride to the reaction suspension at 0° C. The reaction mixture was then partitioned between 340 mL ammounium chloride (sat., aq.) and 370 mL diethyl ether and the organic layer separated and washed further with 1×300 mL water and 1×200 mL brine. The aqueous washes were combined and extracted with 2×200 mL diethyl ether. All of the organic extracts were then combined and dried over sodium sulfate. Concentration of the extracts in vacuo provided a yellow oil, which was purified by flash column chromatography (SiO2, 20% ethyl acetate-hexanes), affording the N-benzyl morpholine product as a yellow oil (926.6 mg, 63%).

Quelle