Reacción #1591079

Ecuación de reacción

16.3

ethyl 2-[(3S)-12-chloro-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(12),2(6),8,10-tetraen-3-yl]acetate

tert-butyl N-(4-hydroxycyclohexyl)carbamate

sodium hydride

→

ethyl 2-[(3S)-12-[(4-[[(tert-butoxy)carbonyl]amino]cyclohexyl)oxy]-7-thia-9,11-diazatricyclo[6.4.0.0^[2,6]]dodeca-1(12),2(6),8,10-tetraen-3-yl]acetate

Rendimiento 49.0%

Disolventes

tetrahydrofuran

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrothe reaction was then quenched with water
2. 2
   Extracciónextracted with ethyl acetate (3×50 mL)
3. 3
   LavadoThe combined organic layers were washed with brine
4. 4
   Secadodried over sodium sulfate
5. 5
   FiltraciónAfter filtration and concentration under reduced pressure
6. 6
   Otropurified

Procedimiento

A solution of tert-butyl N-(4-hydroxycyclohexyl)carbamate (412 mg, 1.91 mmol, 1.10 equiv) in freshly distilled tetrahydrofuran (10 mL) was treated with sodium hydride (60% dispersion in mineral oil, 280 mg, 4.00 equiv) for 1 h at room temperature under nitrogen. To this mixture was then added a solution of 16.3 (510 mg, 1.72 mmol, 1.00 equiv) in dry tetrahydrofuran (5 mL) via syringe. After stirring overnight at room temperature, the reaction was then quenched with water and extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine and dried over sodium sulfate. After filtration and concentration under reduced pressure, the residue was loaded onto a silica gel column with ethyl acetate/petroleum ether (1:2) and purified to afford ethyl 2-[(3S)-12-[(4-[[(tert-butoxy)carbonyl]amino]cyclohexyl)oxy]-7-thia-9,11-diazatricyclo[6.4.0.0^[2,6]]dodeca-1(12),2(6),8,10-tetraen-3-yl]acetate (16.4, 400 mg, 49%) as a yellow oil.

Fuente