反应 #167546

反应方程式

(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

溶剂

DMF H2O

H2O

EtOAc

反应条件

后处理

1. 1
   温度heating
2. 2
   workup.WAITwas continued for 12 h
3. 3
   其他The layers were separated
4. 4
   萃取the aqueous layer extracted 3× with EtOAc
5. 5
   洗涤the combined organic phases washed (H2O x3, brine)
6. 6
   干燥dried (Na2SO4)
7. 7
   过滤filtered
8. 8
   浓缩concentrated
9. 9
   其他The residue was purified by flash (Biotage, 40+M 0-5% MeOH in CH2Cl2; TLC 3% MeOH in CH2Cl2)
10. 10
    其他to afford a light yellow oil which

实验过程

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 x3, 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).

来源