Erythromycin → Flurithromycin

HRID 742178Notes

Reaction equation

HRID 742178 reaction equation
[CH3:1][CH2:2][C@H:3]1[O:18][C:16](=[O:17])[C@H:15]([CH3:19])[C@@H:14]([O:20][C@@H:21]2[O:26][C@@H:25]([CH3:27])[C@H:24]([OH:28])[C@@:23]([O:30][CH3:31])([CH3:29])[CH2:22]2)[C@H:13]([CH3:32])[C@@H:12]([O:33][C@@H:34]2[O:39][C@H:38]([CH3:40])[CH2:37][C@H:36]([N:41]([CH3:43])[CH3:42])[C@H:35]2[OH:44])[C@@:11]([OH:46])([CH3:45])[CH2:10][C@@H:9]([CH3:47])[C:7](=[O:8])[C@H:6]([CH3:48])[C@@H:5]([OH:49])[C@@:4]1([OH:51])[CH3:50].[OH-].[Na+].B([F:60])(OB([O-])[O-])[O-].B(F)(OB([O-])[O-])[O-].B(F)(OB([O-])[O-])[O-].B(F)(OB([O-])[O-])[O-].B(F)(OB([O-])[O-])[O-].B(F)(OB([O-])[O-])[O-].B(F)(OB([O-])[O-])[O-].N1C=CC=CC=1.F[N+]1C=CC=CC=1.F[N+]1C=CC=CC=1.F[N+]1C=CC=CC=1.F[N+]1C=CC=CC=1.F[N+]1C=CC=CC=1.F[N+]1C=CC=CC=1.F[N+]1C=CC=CC=1.F[N+]1C=CC=CC=1.F[N+]1C=CC=CC=1.F[N+]1C=CC=CC=1.F[N+]1C=CC=CC=1.F[N+]1C=CC=CC=1.F[N+]1C=CC=CC=1.F[N+]1C=CC=CC=1.F[N+]1C=CC=CC=1.F[N+]1C=CC=CC=1.F[N+]1C=CC=CC=1.F[N+]1C=CC=CC=1.F[N+]1C=CC=CC=1.F[N+]1C=CC=CC=1.F[N+]1C=CC=CC=1>C(O)(=O)C>[CH3:1][CH2:2][C@H:3]1[O:18][C:16](=[O:17])[C@H:15]([CH3:19])[C@@H:14]([O:20][C@@H:21]2[O:26][C@@H:25]([CH3:27])[C@H:24]([OH:28])[C@@:23]([O:30][CH3:31])([CH3:29])[CH2:22]2)[C@H:13]([CH3:32])[C@@H:12]([O:33][C@@H:34]2[O:39][C@H:38]([CH3:40])[CH2:37][C@H:36]([N:41]([CH3:42])[CH3:43])[C@H:35]2[OH:44])[C@@:11]([OH:46])([CH3:45])[CH2:10][C@@:9]([F:60])([CH3:47])[C:7](=[O:8])[C@H:6]([CH3:48])[C@@H:5]([OH:49])[C@@:4]1([OH:51])[CH3:50]

Participants

5

Reactant 3

HCID 12560ErythromycinHCID 14798Sodium HydroxideHCID 121493828Heptakis(dioxidoboranyloxy(fluoro)borinate);henicosakis(1-fluoropyridin-1-ium);pyridine

Product 1

HCID 71260FlurithromycinYield 11%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Erythromycin A (0.5 g, 0.681 mmole) was dissolved in glacial acetic acid (4 mL) at room temperature and stirred for 2 hours. The pH of the mixture was adjusted to 4.3 with 6N sodium hydroxide (approx. 1.2 mL) while the temperature was maintained below 20° C. N-fluoropyridinium pyridine heptafluorodiborate (0.25 g, 0.75 mmole) was added and stirring continued for an additional 2 hours at 22° C. The reaction was worked up in the same manner as Example 1 to afford an 11% yield of crude flurithromycin. Although the yield was only 11%, this example demonstrates operation of the invention with N-F fluorinating agents derived from pyridine since with a co-solvent no flurithromycin is formed. (See Comparative Example 4).

Workup

  1. temperaturewas maintained below 20° C
  2. stirringstirring
  3. waitcontinued for an additional 2 hours at 22° C

Sources & evidence

ORD record
ord-e9d8be5613434c3981bde3e4ff13164c
Source dataset
uspto-grants-1996_09
Patent number
US05552533

Reaction notes

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