Cesium fluoride → 1-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl)-4-chloro-3-(5-(6-fluoro-3-pyridyl)-2-thienylmethyl)benzene

HRID 570986Notes

Reaction equation

HRID 570986 reaction equation
[C:1]([O:4][C@@H:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@@H:8]([CH2:19][O:20][C:21](=[O:23])[CH3:22])[O:7][C@H:6]1[C:24]1[CH:29]=[CH:28][C:27]([Cl:30])=[C:26]([CH2:31][C:32]2[S:33][C:34](Br)=[CH:35][CH:36]=2)[CH:25]=1)(=[O:3])[CH3:2].[F:38][C:39]1[CH:44]=[CH:43][C:42](B(O)O)=[CH:41][N:40]=1.[F-].[Cs+].C(=O)([O-])O.[Na+]>COCCOC>[C:1]([O:4][C@@H:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@@H:8]([CH2:19][O:20][C:21](=[O:23])[CH3:22])[O:7][C@H:6]1[C:24]1[CH:29]=[CH:28][C:27]([Cl:30])=[C:26]([CH2:31][C:32]2[S:33][C:34]([C:42]3[CH:41]=[N:40][C:39]([F:38])=[CH:44][CH:43]=3)=[CH:35][CH:36]=2)[CH:25]=1)(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 25953Cesium fluorideHCID 516892Sodium BicarbonateHCID 2783397(6-Fluoropyridin-3-yl)boronic acidHCID 600412891-(2,3,4,6-Tetra-O-acetyl-beta-D-glucopyranosyl)-3-(5bromo-2-thienylmethyl)-4-chlorobenzene

Product 1

HCID 666074991-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl)-4-chloro-3-(5-(6-fluoro-3-pyridyl)-2-thienylmethyl)benzeneYield 60.1%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

A suspension of 1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-4-chloro-3-(5-bromo-2-thienylmethyl)benzene (13.5 g; prepared as described in PCT Publication WO 2005/012326), 2-fluoropyridine-5-boronic acid (Frontier Scientific, 4.63 g), cesium fluoride (19.96 g) and tetrakis(triphenylphosphin)palladium(0) (2.53 g) in 1,2-dimethoxyethane (200 ml) was refluxed for 1.5 hours. The reaction mixture was poured into a saturated aqueous sodium hydrogen carbonate solution, and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was dissolved in ethyl acetate, and the mixture was treated with activated carbon and filtered through aminosilane-treated silica gel (27 ml) pad. The filtrate was evaporated under reduced pressure, and the residue was purified by silica gel flash column chromatography (hexane:ethyl acetate:dichloromethane 2:1:1) and recrystallized from methanol to yield 1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-4-chloro-3-(5-(6-fluoro-3-pyridyl)-2-thienylmethyl)benzene (8.33 g) as a colorless crystal.

Workup

  1. temperaturewas refluxed for 1.5 hours
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over sodium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. dissolutionThe residue was dissolved in ethyl acetate
  7. additionthe mixture was treated with activated carbon
  8. filtrationfiltered through aminosilane-
  9. additiontreated silica gel (27 ml) pad
  10. customThe filtrate was evaporated under reduced pressure
  11. customthe residue was purified by silica gel flash column chromatography (hexane:ethyl acetate:dichloromethane 2:1:1)
  12. customrecrystallized from methanol

Sources & evidence

ORD record
ord-f3dbbf0c9dd34f43b1ed71dba3663f59
Source dataset
uspto-grants-2015_05
Patent number
US09024009B2

Reaction notes

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