Dichloromethane → Flurithromycin

HRID 742180Notes

Reaction equation

HRID 742180 reaction equation
[CH3:1][CH2:2][C@H:3]1[O:19][C:17](=[O:18])[C@H:16]([CH3:20])[C@@H:15]([O:21][C@@H:22]2[O:27][C@@H:26]([CH3:28])[C@H:25]([OH:29])[C@@:24]([O:31][CH3:32])([CH3:30])[CH2:23]2)[C@H:14]([CH3:33])[C@@H:13]([O:34][C@@H:35]2[O:40][C@H:39]([CH3:41])[CH2:38][C@H:37]([N:42]([CH3:44])[CH3:43])[C@H:36]2[OH:45])[C@:11]2([CH3:46])[O:12][C@@:7]3([C@H:9]([CH3:47])[CH2:10]2)[O:8][C@:4]1([CH3:50])[C@H:5]([OH:49])[C@H:6]3[CH3:48].[OH-:51].[Na+].C1C=CC(S(N(S(C2C=CC=CC=2)(=O)=O)[F:63])(=O)=O)=CC=1.C(Cl)Cl>C(O)(=O)C.O>[CH3:1][CH2:2][C@H:3]1[O:19][C:17](=[O:18])[C@H:16]([CH3:20])[C@@H:15]([O:21][C@@H:22]2[O:27][C@@H:26]([CH3:28])[C@H:25]([OH:29])[C@@:24]([O:31][CH3:32])([CH3:30])[CH2:23]2)[C@H:14]([CH3:33])[C@@H:13]([O:34][C@@H:35]2[O:40][C@H:39]([CH3:41])[CH2:38][C@H:37]([N:42]([CH3:44])[CH3:43])[C@H:36]2[OH:45])[C@@:11]([OH:12])([CH3:46])[CH2:10][C@@:9]([F:63])([CH3:47])[C:7](=[O:51])[C@H:6]([CH3:48])[C@@H:5]([OH:49])[C@@:4]1([OH:8])[CH3:50]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 14798Sodium Hydroxide2×HCID 588007N-FluorobenzenesulfonimideHCID 21680609(1S,2R,3R,4R,5R,8R,9S,10S,11R,12R,14R)-11-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyl-tetrahydropyran-2-yl]oxy-5-ethyl-3-hydroxy-9-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyl-tetrahydropyran-2-yl]oxy-2,4,8,10,12,14-hexamethyl-6,15,16-trioxatricyclo[10.2.1.11,4]hexadecan-7-one

Product 1

HCID 71260Flurithromycin

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Procedure

Anhydroerythromycin A (1 g, 1.4 mmole) was dissolved in glacial acetic acid (4-mL) at room temperature and the pH of the mixture was adjusted to 4.3 with 6N sodium hydroxide (approx. 2.5 mL) while the temperature was maintained below 20° C. N-fluorobenzenesulfonimide (0.44 g, 1.4 mmole) was added and stirring continued for an additional 18 hours at 22° C. Methylene chloride (10 mL) was added, the solution placed in an ice bath while the pH of the mixture was adjusted to 9 with 6N sodium hydroxide (approx. 17 mL) and the temperature maintained below 20° C. Next, water (10 mL) was added, the layers separated and the aqueous layer washed an additional two times with methylene chloride (10 mL each). The combined organic phases were washed 2 to 4 times with 5% sodium hydroxide (10 mL each) and dried over magnesium sulfate. After filtration, the organic phase was concentrated under vacuum at room temperature to afford 0.88 g of crude flurithromycin. The crude material was dissolved in ethanol concentrated to 2 mL. This process was repeated two more times. After standing at 0° C. for one night, the product was filtered under vacuum, washed with 0.5 mL cold ethanol and dried under vacuum at 40° C. to afford 0.53 g (51% yield) of flurithromycin.

Workup

  1. temperaturewas maintained below 20° C
  2. customthe solution placed in an ice bath while the pH of the mixture
  3. temperaturethe temperature maintained below 20° C
  4. customthe layers separated
  5. washthe aqueous layer washed an additional two times with methylene chloride (10 mL each)
  6. washThe combined organic phases were washed 2 to 4 times with 5% sodium hydroxide (10 mL each)
  7. dry with materialdried over magnesium sulfate
  8. filtrationAfter filtration
  9. concentrationthe organic phase was concentrated under vacuum at room temperature

Sources & evidence

ORD record
ord-b6292bf4af034962bff5cf194b5e31a6
Source dataset
uspto-grants-1996_09
Patent number
US05552533

Reaction notes

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