反応 #82438

反応方程式

NaOH

bromoacetic acid

NaOH

α-[(phenylmethoxy)methyl]-1,4,7,10-tetraazacyclododecan-1-acetamide trihydrochloride

NaOH

→

desired product

収率 150.0%

10-[2-[[2-(2-hydroxyethoxy)ethyl]amino]-2-oxo-1-[(phenylmethoxy)methyl]ethyl]-1,4,7,10-tetraazacyclododecan-1,4,7-triacetic acid

収率 150.0%

溶媒

H2O

H2O

反応条件

後処理

1. 1
   温度The reaction mixture is heated to 50° C. for 48 h
2. 2
   温度After cooling at room temperature
3. 3
   ろ過the mixture is filtered on a MilliporeR
4. 4
   ろ過filter
5. 5
   workup.ADDITIONdiluted to 1.5 L with H2O
6. 6
   濃縮is concentrated under vacuum
7. 7
   その他to give an oily residue which
8. 8
   その他to give a glassy solid
9. 9
   その他The solid is triturated
10. 10
    workup.DISSOLUTIONdissolved with AcOEt (200 mL)
11. 11
    ろ過filtered
12. 12
    その他dried again
13. 13
    workup.DISSOLUTIONThe crude product is dissolved in H2O (150 mL)
14. 14
    洗浄a gradient elution with H2O-MeOH
15. 15
    workup.ADDITIONThe fractions containing the pure product
16. 16
    その他are collected
17. 17
    濃縮concentrated under vacuum

実験手順

To a solution of 45.5 g of bromoacetic acid (0.327 mol) in 140 mL of H2O, kept under stirring at 0° C., 31.5 mL of 10N NaOH (0.315 mol) are added in 1 h to pH 6. The resulting solution is added drop by drop to a solution of 46 g of N-[2-(2-hydroxyethoxy)ethyl)]-α-[(phenylmethoxy)methyl]-1,4,7,10-tetraazacyclododecan-1-acetamide trihydrochloride (0.084 mol) in H2O (100 mL) and, at a constant reaction temperature of 0° C., 10N NaOH is slowly added to pH 10. The reaction mixture is heated to 50° C. for 48 h and 50 mL of 10N NaOH (0.5 mol) are added to keep a constant pH of 10. After cooling at room temperature, the mixture is filtered on a MilliporeR filter, neutralized with 37%HCl (w/w), diluted to 1.5 L with H2O and electrodialyzed. When the electrodialysis is over, the solution is concentrated under vacuum to give an oily residue which is placed into a drier to give a glassy solid. The solid is triturated and dissolved with AcOEt (200 mL), filtered and dried again. The crude product is dissolved in H2O (150 mL) and percolated on Amberlite® XAD 16 resin (1000 mL) performing a gradient elution with H2O-MeOH. The fractions containing the pure product are collected and concentrated under vacuum to give 38.83 g of the desired product (0.063 mol).

出典