Reacción #2122535

Ecuación de reacción

ClCO2Me

(S)-benzyl 3-(1-benzyl-1H-1,2,3-triazol-4-yl)-2-(tert-butoxycarbonylamino)propanoate

TFA

HCl

NaHCO3

→

(S)-benzyl 3-(1-benzyl-1H-1,2,3-triazol-4-yl)-2-(methoxycarbonylamino)propanoate

Disolventes

CH2Cl2

THF H2O

H2O EtOAc

Condiciones de reacción

Tratamiento posterior

1. 1
   ConcentraciónThe mixture was concentrated in vacuo
2. 2
   Otroto give a colorless oil which
3. 3
   Temperaturacooled to 0° C
4. 4
   workup.STIRRINGAfter stirring for 1.5 h the mixture
5. 5
   OtroThe layers were separated
6. 6
   Extracciónthe aq phase extracted 2× with EtOAc
7. 7
   LavadoThe combined org layers were washed (H2O, brine)
8. 8
   Secadodried (Na2SO4)
9. 9
   Filtraciónfiltered
10. 10
    Concentraciónconcentrated in vacuo
11. 11
    Otroto give a colorless oil (505.8 mg, 111%, NMR
12. 12
    Otroas is without further purification

Procedimiento

A solution of (S)-benzyl 3-(1-benzyl-1H-1,2,3-triazol-4-yl)-2-(tert-butoxycarbonylamino)propanoate (0.52 g, 1.15 mmol) in CH2Cl2 was added TFA (4 mL). The mixture was allowed to stir at room temperature for 2 h. The mixture was concentrated in vacuo to give a colorless oil which solidified on standing. This material was dissolved in THF-H2O and cooled to 0° C. Solid NaHCO3 (0.25 g, 3.00 mmol) was added followed by ClCO2Me (0.25 mL, 3.25 mmol). After stirring for 1.5 h the mixture was acidified to pH-2 with 6N HCl and then poured into H2O-EtOAc. The layers were separated and the aq phase extracted 2× with EtOAc. The combined org layers were washed (H2O, brine), dried (Na2SO4), filtered, and concentrated in vacuo to give a colorless oil (505.8 mg, 111%, NMR suggested the presence of an unidentified impurity) which solidified while standing on the pump. The material was used as is without further purification. 1HNMR (400 MHz, DMSO-d6) δ 7.87 (s, 1H), 7.70 (d, J=8.1 Hz, 1H), 7.27-7.32 (m, 10H), 5.54 (s, 2H), 5.10 (d, J=12.7 Hz, 1H), 5.06 (d, J=12.7 Hz, 1H), 4.32-4.37 (m, 1H), 3.49 (s, 3H), 3.09 (dd, J=5.6, 14.7 Hz, 1H), 2.98 (dd, J=9.6, 14.7 Hz, 1H). LCMS: Anal. Calcd. for C21H22N4O4: 394; found: 395 (M+H)+.

Fuente