Triethylamine → N-methyl-N-carboxymethylglycylthyroxine methyl ester

HRID 2418403Notes

Reaction equation

HRID 2418403 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:26])[C@H:5]([CH2:7][C:8]1[CH:15]=[C:13]([I:14])[C:12]([O:16][C:17]2[CH:24]=[C:22]([I:23])[C:21]([OH:25])=[C:19]([I:20])[CH:18]=2)=[C:10]([I:11])[CH:9]=1)[NH2:6].C(N(CC)CC)C.[CH3:34][N:35]1[CH2:41][C:40](=[O:42])[O:39][C:37](=[O:38])[CH2:36]1>CN(C)C=O.O1CCCC1>[CH3:2][O:3][C:4](=[O:26])[C@H:5]([CH2:7][C:8]1[CH:9]=[C:10]([I:11])[C:12]([O:16][C:17]2[CH:18]=[C:19]([I:20])[C:21]([OH:25])=[C:22]([I:23])[CH:24]=2)=[C:13]([I:14])[CH:15]=1)[NH:6][C:40](=[O:42])[CH2:41][N:35]([CH3:34])[CH2:36][C:37]([OH:39])=[O:38]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 13911220Methyl thyroxinate hydrochlorideHCID 143203244-Methylmorpholine-2,6-dione

Product 1

HCID 22827706N-methyl-N-carboxymethylglycylthyroxine methyl esterYield 103.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

In 15 ml of dimethylformamide (DMF), 2 g of thyroxine methyl ester hydrochloride was dissolved and 500 μl of triethylamine was added to the resulting solution. After 10 minutes passed, a solution of 0.55 g of N-methyliminodiacetic acid anhydride in 5 ml of tetrahydrofuran (THF) was added to the mixture. After completion of the reacton, the reaction mixture was condensed using a rotary evaporator and the residue was dissolved in 50 ml of THF. Further, 150 ml of ethyl acetate was added to the solution. After stirring the mixture by shaking, the ethyl acetate layer was taken out and washed three times with distilled water and then once with a saturated aqueous sodium chloride solution. After the ethyl acetate layer was dried over anhydrous sodium sulfate, the supernatant was condensed using a rotary evaporator. To the residue, 20 ml of THF was added and then a small quantity of n-hexane was added to form precipitates. The precipitates were subjected to suction filtration to obtain white crystals. The crystals were dried in a dessicator under reduced pressure to obtain 2.3 g of white crystals. The yield was 69%.

Workup

  1. customcondensed
  2. customa rotary evaporator
  3. dissolutionthe residue was dissolved in 50 ml of THF
  4. additionFurther, 150 ml of ethyl acetate was added to the solution
  5. stirringby shaking
  6. washwashed three times with distilled water
  7. dry with materialAfter the ethyl acetate layer was dried over anhydrous sodium sulfate
  8. customcondensed
  9. customa rotary evaporator
  10. additionTo the residue, 20 ml of THF was added
  11. additiona small quantity of n-hexane was added
  12. customto form
  13. customprecipitates
  14. filtrationThe precipitates were subjected to suction filtration
  15. customto obtain white crystals
  16. customThe crystals were dried in a dessicator under reduced pressure

Sources & evidence

ORD record
ord-30cb0ae20d7d4b29a910efa5babdcb85
Source dataset
uspto-grants-1984_09
Patent number
US04472498

Reaction notes

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