Bromoacetic Acid → 10-[2-[[2-(2-Hydroxyethoxy)ethyl]amino]-2-oxo-1-[(phenylmethoxy)methyl]ethyl]-1,4,7,10-tetraazacyclododecan-1,4,7-triacetic acid

HRID 54160Notes

Reaction equation

HRID 54160 reaction equation
Br[CH2:2][C:3]([OH:5])=[O:4].[OH-:6].[Na+].Cl.Cl.Cl.[C:11]1([CH2:17][O:18][CH2:19][CH:20]([N:24]2[CH2:35][CH2:34][NH:33][CH2:32][CH2:31][NH:30][CH2:29][CH2:28][NH:27][CH2:26][CH2:25]2)[C:21]([NH2:23])=[O:22])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>O>[OH:6][CH2:11][CH2:17][O:18][CH2:19][CH2:20][NH:23][C:21](=[O:22])[CH:20]([N:24]1[CH2:35][CH2:34][N:33]([CH2:2][C:3]([OH:5])=[O:4])[CH2:32][CH2:31][N:30]([CH2:2][C:3]([OH:5])=[O:4])[CH2:29][CH2:28][N:27]([CH2:2][C:3]([OH:5])=[O:4])[CH2:26][CH2:25]1)[CH2:19][O:18][CH2:17][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

5

Reactant 3

HCID 6227Bromoacetic AcidHCID 14798Sodium Hydroxide3×HCID 86750719alpha-[(Phenylmethoxy)methyl]-1,4,7,10-tetraazacyclododecan-1-acetamide trihydrochloride

Product 1

HCID 1971050910-[2-[[2-(2-Hydroxyethoxy)ethyl]amino]-2-oxo-1-[(phenylmethoxy)methyl]ethyl]-1,4,7,10-tetraazacyclododecan-1,4,7-triacetic acidYield 150%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
0 °C

Procedure

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).

Workup

  1. temperatureThe reaction mixture is heated to 50° C. for 48 h
  2. temperatureAfter cooling at room temperature
  3. filtrationthe mixture is filtered on a MilliporeR
  4. filtrationfilter
  5. additiondiluted to 1.5 L with H2O
  6. concentrationis concentrated under vacuum
  7. customto give an oily residue which
  8. customto give a glassy solid
  9. customThe solid is triturated
  10. dissolutiondissolved with AcOEt (200 mL)
  11. filtrationfiltered
  12. customdried again
  13. dissolutionThe crude product is dissolved in H2O (150 mL)
  14. washa gradient elution with H2O-MeOH
  15. additionThe fractions containing the pure product
  16. customare collected
  17. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-9a7c0abf2055454299b30f5fa8233fa9
Source dataset
uspto-grants-1997_04
Patent number
US05622688

Reaction notes

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