Reacción #89730

Ecuación de reacción

Lithium hexamethyldisilazide

1-benzyl 4-methyl(2S)-2-[benzyl((2R)-2-(1-ethoxyethoxy)-3-[(4-methylphenyl)sulfonyl]oxypropyl)amino]succinate

toluene

→

product

Rendimiento 78.2%

2-benzyl 3-methyl(2S,3S,5S)-1-benzyl-5-(1-ethoxyethoxy)piperidine-2,3-dicarboxylate

Rendimiento 78.2%

Disolventes

tetrahydrofuran

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturato warm up to at 0 Celsius gradually
2. 2
   workup.STIRRINGstirred at 0 Celsius for 30 min
3. 3
   OtroAfter quenched with aq ammonium chloride
4. 4
   Extracciónthe mixture was extracted with ethyl acetate
5. 5
   LavadoThe combined organic layers were washed with water, brine
6. 6
   Secadodried (sodium sulfate)
7. 7
   Concentraciónconcentrated
8. 8
   Otroto dry
9. 9
   OtroThe residue was purified on silica gel column
10. 10
    Lavadoeluting with 0 to 20% EtOAc in hexane

Procedimiento

To a solution of 1-benzyl 4-methyl(2S)-2-[benzyl((2R)-2-(1-ethoxyethoxy)-3-[(4-methylphenyl)sulfonyl]oxypropyl)amino]succinate (34.30 g, 0.05464 mol) in a mixture of tetrahydrofuran (90.0 mL, 1.11 mol) and toluene (470.0 mL, 4.412 mol) at −78 Celsius was added 1.00 M of Lithium hexamethyldisilazide in tetrahydrofuran (65.6 mL). The resulting mixture was stirred at −78 Celsius overnight, and then allowed to warm up to at 0 Celsius gradually and stirred at 0 Celsius for 30 min. After quenched with aq ammonium chloride, the mixture was extracted with ethyl acetate. The combined organic layers were washed with water, brine, and dried (sodium sulfate), and concentrated to dry. The residue was purified on silica gel column, eluting with 0 to 20% EtOAc in hexane, to yield the cyclized product (19.47 g, 78.2%). MS (ESI): (M+H)+=456.0.

Fuente