Hydrochloric Acid → N-Acetylthyroxine

HRID 1708611Notes

Reaction equation

HRID 1708611 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>CCO.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 23666112Levothyroxine Sodium

Product 1

HCID 20638380N-AcetylthyroxineYield 90%

Reagents, catalysts & solvents 4

HCID 702EthanolSolvent2×HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 14798Sodium HydroxideSolvent

Procedure

L-Thyroxine sodium salt, pentahydrate (1)(10 g, 11 mmol)was nearly completely dissolved in 400 mL of EtOH/2 N NH4OH (1/1, v/v), filtered, and flitrate 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 EtOH and 41 mL of 1 N 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. additionflitrate 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. waitto stand at 4° C. for 16 hours
  10. customThe resulting precipitate was isolated by vacuum filtration
  11. customdried under high vacuum

Sources & evidence

ORD record
ord-66b54c69fded483e9c868f07e31c3120
Source dataset
uspto-grants-1994_10
Patent number
US05359093

Reaction notes

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