Reacción #6174

Ecuación de reacción

NH4Cl

aldehyde

(2R,3S)-N-[(tert-Butyloxy) Carbonyl]-3-amino-4-cyclohexyl-2-(triisopropylsilyloxy) butanal

propargyl bromide

toluene

→

title compound

(4S,5R,6S)-N-[(tert-Butyloxy)carbonyl]-6-amino-7-cyclohexyl-4-hydroxy-5-(triisopropylsilyloxy)hept-1-yne

Disolventes

diethyl ether

diethyl ether

diethyl ether

diethyl ether

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONseveral drops were added to the reaction mixture
2. 2
   workup.ADDITIONwas added to the funnel solution
3. 3
   workup.ADDITIONThe funnel solution was added dropwise while the reaction solution
4. 4
   workup.STIRRINGThe yellow, opaque mixture was stirred at room temperature for 2 hours
5. 5
   TemperaturaThe mixture was cooled to about 0° C. with an ice-water bath
6. 6
   OtroThe organic layer was collected
7. 7
   Extracciónthe aqueous layer was extracted with diethyl ether (10 mL)
8. 8
   LavadoThe combined organic layers were washed with H2O (10 mL) and brine
9. 9
   Secadodried over MgSO4
10. 10
    ConcentraciónThe filtrate was concentrated
11. 11
    Otropurified by medium pressure column chromatography (10% EtOH in hexane, silica gel, Rf 0.20)

Procedimiento

To a dry flask under an N2 atmosphere was added Mg (0.40 g, 6.4 mmol), HgCl2 (0.03 g) and anhydrous diethyl ether (4 mL). A solution of 80% propargyl bromide in toluene (1.83 mL, 16.4 mmol) was added to an addition funnel and several drops were added to the reaction mixture. After the reaction was initiated, anhydrous diethyl ether (10 mL) was added to the reaction flask and anhydrous diethyl ether (10 mL) was added to the funnel solution. The funnel solution was added dropwise while the reaction solution was cooled with a 10° C. bath. The white, opaque mixture was stirred at room temperature for 45 minutes and then a solution of aldehyde of Step 4 (2.05 g, 4.64 mmol) in anhydrous diethyl ether (10 mL) was added dropwise. The yellow, opaque mixture was stirred at room temperature for 2 hours. The mixture was cooled to about 0° C. with an ice-water bath and a saturated NH4Cl solution (25 mL) was added dropwise. The organic layer was collected and the aqueous layer was extracted with diethyl ether (10 mL). The combined organic layers were washed with H2O (10 mL) and brine and then dried over MgSO4. The filtrate was concentrated and purified by medium pressure column chromatography (10% EtOH in hexane, silica gel, Rf 0.20) to give the title compound as a clear, pale yellow liquid (1.49 g, 65% yield). The 1H and 13C NMR spectral data were consistent with the proposed structure.

Fuente