Reacción #51487

Ecuación de reacción

methyl 4-Boc-piperazine-2-acetate

FMOC-Cl

NaOH

HCl

NaOH

→

4-Boc-1-Fmoc-piperazine-2-acetic acid

Rendimiento 91.7%

Disolventes

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaThe reaction was cooled to 0° C.
2. 2
   workup.ADDITIONwas added
3. 3
   workup.STIRRINGThe reaction was stirred at room temperature for 6 hours
4. 4
   ExtracciónThe reaction was extracted twice
5. 5
   Lavadothe combined organic layers were washed with brine
6. 6
   Secadodried over MgSO4
7. 7
   Concentraciónconcentrated in vacuo

Procedimiento

A portion (5.2 g; 20 mmol) of the methyl 4-Boc-piperazine-2-acetate product from the previous step was combined with 60 mL of THF and 60 mL of 1 N NaOH (aqueous) and stirred at room temperature for 6 hours to saponify the methyl ester. The reaction was cooled to 0° C., adjusted to pH 9-10 with 10% HCl(aqueous), and 5.2 g (20 mmol) of FMOC-Cl was added. The reaction was stirred at room temperature for 6 hours, (adding 1 N NaOH (aqueous) to maintain pH 9-10) 1 hour, then acidified with 10% HCl to pH=1. The reaction was extracted twice, the combined organic layers were washed with brine, dried over MgSO4 and concentrated in vacuo to give 8.56 g of the desired 4-Boc-1-Fmoc-piperazine-2-acetic acid (the compound of formula (XXIV)); 1H NMR (CDCl3) δ 1.4 (s,9), 2.5-3.0 (m,5) 3.9-4.2 (m,6), 4.5 (m,1), 7-25 (t,4), 7.32 (t,4), 7.48 (d,4), 7.75 (d, 4).

Fuente