Reacción #2122534

Ecuación de reacción

(S)-benzyl 2-(tert-butoxycarbonylamino)pent-4-ynoate

sodium ascorbate

NaN3

NaN3

BnBr

→

desired product

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

Disolventes

DMF H2O

H2O

EtOAc

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturaheating
2. 2
   workup.WAITwas continued for 12 h
3. 3
   OtroThe layers were separated
4. 4
   Extracciónthe aqueous layer extracted 3× with EtOAc
5. 5
   Lavadothe combined organic phases washed (H2O×3, brine)
6. 6
   Secadodried (Na2SO4)
7. 7
   Filtraciónfiltered
8. 8
   Concentraciónconcentrated
9. 9
   OtroThe residue was purified by flash (Biotage, 40+M 0-5% MeOH in CH2Cl2; TLC 3% MeOH in CH2Cl2)
10. 10
    Otroto afford a light yellow oil which

Procedimiento

To a mixture of (S)-benzyl 2-(tert-butoxycarbonylamino)pent-4-ynoate (0.50 g, 1.65 mmol), sodium ascorbate (0.036 g, 0.18 mmol), CuSO4-5H2O (0.022 g, 0.09 mmol) and NaN3 (0.13 g, 2.1 mmol) in DMF-H2O (5 mL, 4:1) at rt was added BnBr (0.24 mL, 2.02 mmol) and the mixture was warmed to 65° C. After 5 h LCMS indicated low conversion. A further portion of NaN3 (100 mg) was added and heating was continued for 12 h. The reaction was poured into EtOAc and H2O and shaken. The layers were separated and the aqueous layer extracted 3× with EtOAc and the combined organic phases washed (H2O×3, brine), dried (Na2SO4), filtered, and concentrated. The residue was purified by flash (Biotage, 40+M 0-5% MeOH in CH2Cl2; TLC 3% MeOH in CH2Cl2) to afford a light yellow oil which solidified on standing (748.3 mg, 104%). The NMR was consistent with the desired product but suggests the presence of DMF. The material was used as is without further purification. 1HNMR (400 MHz, DMSO-d6) δ 7.84 (s, 1H), 7.27-7.32 (m, 10H), 5.54 (s, 2H), 5.07 (s, 2H), 4.25 (m, 1H), 3.16 (dd, J=1.0, 5.3 Hz, 1H), 3.06 (dd, J=5.3, 14.7 Hz), 2.96 (dd, J=9.1, 14.7 Hz, 1H), 1.31 (s, 9H).

Fuente