Hydrochloric Acid → N-Acetylthyroxine

HRID 265216

Reaction equation

HRID 265216 reaction equation
[Na+].[NH2:2][C@H:3]([C:23]([O-:25])=[O:24])[CH2:4][C:5]1[CH:12]=[C:10]([I:11])[C:9]([O:13][C:14]2[CH:21]=[C:19]([I:20])[C:18]([OH:22])=[C:16]([I:17])[CH:15]=2)=[C:7]([I:8])[CH:6]=1.[C:26](OC(=O)C)(=[O:28])[CH3:27].Cl>[NH4+].[OH-].CN(C=O)C.O.[OH-].[Na+]>[C:26]([NH:2][C@H:3]([C:23]([OH:25])=[O:24])[CH2:4][C:5]1[CH:6]=[C:7]([I:8])[C:9]([O:13][C:14]2[CH:15]=[C:16]([I:17])[C:18]([OH:22])=[C:19]([I:20])[CH:21]=2)=[C:10]([I:11])[CH:12]=1)(=[O:28])[CH3:27]

Participants

8

Reactant 3

HCID 313Hydrochloric AcidHCID 7918Acetic AnhydrideHCID 23666112L-Thyroxine monosodium salt

Product 1

HCID 20638380N-AcetylthyroxineYield 90%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 14798Sodium HydroxideSolventHCID 14923Ammonium HydroxideSolvent

Procedure

L-Thyroxine sodium salt, pentahydrate (1) (10 g, 11 mmol) was nearly completely dissolved in 400 mL of ETCH/2N NH4OH (1/1, v/v), filtered, and filtrate poured into 425 mL of 5% HCl. The resulting precipitate was isolated by vacuum filtration and dried under high vacuum to afford a white solid. This material was dissolved in 160 mL DMF, 100 mL (1.06 mol) of acetic anhydride added, and reaction stirred for 1.5 hours, then diluted with 850 mL H2O and allowed to stand at 4° C. for 16 hours. The resulting precipitate was isolated by filtration, then dissolved in 350 mL EtCH and 41 mL of 1N NaOH, stirred for 2.5 hours, 680 mL of 5% HCl added, and mixture allowed to stand at 4° C. for 16 hours. The resulting precipitate was isolated by vacuum filtration and dried under high vacuum to yield 8.1 g (90%) of the desired N-acetyl L-thyroxine (5) as a white solid; 1H NMR (200 MHz, CD3OD) d 7.8 (s, 2H), 7.1 (s, 2H), 4.6-4.7 (m, 1H), 2.8-3.0 (m, 2H), 2.0 (s, 3H); mass spec (FAB) (M+H)+820.

Workup

  1. filtrationv/v), filtered
  2. additionfiltrate poured into 425 mL of 5% HCl
  3. customThe resulting precipitate was isolated by vacuum filtration
  4. customdried under high vacuum
  5. customto afford a white solid
  6. customreaction
  7. waitto stand at 4° C. for 16 hours
  8. customThe resulting precipitate was isolated by filtration
  9. stirringstirred for 2.5 hours
  10. waitto stand at 4° C. for 16 hours
  11. customThe resulting precipitate was isolated by vacuum filtration
  12. customdried under high vacuum

Sources & evidence

ORD record
ord-2f053ae5761b40eca8afc9aa31317f8c
Source dataset
uspto-grants-1997_07
Patent number
US05648272

Linked notes

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