Water → O-acetyl thyroxine

HRID 233428

Reaction equation

HRID 233428 reaction equation
[NH2:1][C@H:2]([C:22]([OH:24])=[O:23])[CH2:3][C:4]1[CH:11]=[C:9]([I:10])[C:8]([O:12][C:13]2[CH:20]=[C:18]([I:19])[C:17]([OH:21])=[C:15]([I:16])[CH:14]=2)=[C:6]([I:7])[CH:5]=1.[C:25](OC(=O)C)(=[O:27])[CH3:26].O>C1COCC1.CN(C)C1C=CN=CC=1>[C:25]([O:23][C:22](=[O:24])[C@H:2]([CH2:3][C:4]1[CH:5]=[C:6]([I:7])[C:8]([O:12][C:13]2[CH:14]=[C:15]([I:16])[C:17]([OH:21])=[C:18]([I:19])[CH:20]=2)=[C:9]([I:10])[CH:11]=1)[NH2:1])(=[O:27])[CH3:26]

Participants

6

Reactant 3

HCID 962WaterHCID 5819ThyroxineHCID 7918Acetic Anhydride

Product 1

HCID 86748204O-acetyl thyroxineYield 115.5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

The N-FMOC protected L-Thyroxine (26.3 g, 23.2 mmol) was dissolved in 150 mL THF, 3.28 mL (34.8 mmol) of acetic anhydride added, 283 mg (2.32 mmol) of 4-dimethylaminopyridine added, and reaction stirred under N2 for 45 minutes, then poured into 400 mL H2O and extracted with CHCl3 (3×400 mL). The CHCl3 extracts were combined, dried over Na2SO4, and solvent removed in vacuo. The residue was then purified by silica gel column chromatography, eluting with CH2Cl2 /MeOH/HOAc (90/10/0.4, v/v), to yield 21.95 g (91%) of the desired O-acetyl thyroxine as a beige solid; 1H NMR (300 MHz, DMSO-D6) d 7.12-7.91 (m, 12H), 4.07-4.31 (m, 4H), 3.07-3.19 (m, 1H), 2.82 (t, 1H), 2.29-2.40 (m, 3H); mass spec (FAB) (M+H)+ 1042.

Workup

  1. customreaction
  2. extractionextracted with CHCl3 (3×400 mL)
  3. dry with materialdried over Na2SO4, and solvent
  4. customremoved in vacuo
  5. customThe residue was then purified by silica gel column chromatography
  6. washeluting with CH2Cl2 /MeOH/HOAc (90/10/0.4

Sources & evidence

ORD record
ord-964dc7dfe9564806934be0f85bb4fb63
Source dataset
uspto-grants-1997_01
Patent number
US05593896

Linked notes

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