1,1'-Carbonyldiimidazole → 1-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl)-4-chloro-3(5-(4-cyano-3-fluorophenyl)-2-thienylmethyl)benzene

HRID 1514490Notes

Reaction equation

HRID 1514490 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]([C:37]3[CH:42]=[CH:41]C(=NO)[CH:39]([F:45])[CH:38]=3)=[CH:35][CH:36]=2)[CH:25]=1)(=[O:3])[CH3:2].C([N:53]1[CH:57]=[CH:56]N=C1)(N1C=CN=C1)=O>C(Cl)(Cl)Cl.C(OCC)(=O)C.O>[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:37]3[CH:42]=[CH:41][C:56]([C:57]#[N:53])=[C:39]([F:45])[CH:38]=3)=[CH:35][CH:36]=2)[CH:25]=1)(=[O:3])[CH3:2]

Participants

6

Reactant 2

HCID 682631,1'-Carbonyldiimidazole2×HCID 866010761-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl)-4-chloro-3(5-(4-hydroxyimino-3-fluorophenyl)-2-thienylmethyl)benzene

Product 1

HCID 666086331-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl)-4-chloro-3(5-(4-cyano-3-fluorophenyl)-2-thienylmethyl)benzeneYield 91.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6212ChloroformSolventHCID 8857Ethyl AcetateSolvent

Procedure

1-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyl)-4-chloro-3-(5-(3-fluoro-4-formylphenyl)-2-thienylmethyl)benzene (272 mg) obtained in Example 180-(1) was dissolved in N-methyl-2-pyrrolidone (10 ml) and added thereto was hydroxylamine hydrochloride (34 mg). The mixture was heated under stirring at 117° C. overnight. The reaction solution was cooled and diluted with ethyl acetate and water. The organic layer was washed with water and successively washed with brine. After drying over magnesium sulfate, the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=3:1-2:1) to give 1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-4-chloro-3-(5-(4-hydroxyimino-3-fluorophenyl)-2-thienylmethyl)benzene (177 mg) as colorless caramel. APCI-Mass m/Z 693/695 (M+NH4). (2) The above 1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-4-chloro-3-(5-(4-hydroxyimino-3-fluorophenyl)-2-thienylmethyl)benzene (175 mg) was dissolved in chloroform (5 ml) and added thereto was 1,1′-carbonyldiimidazole (46 mg). The mixture was stirred at room temperature overnight. 1,1′-Carbonyldiimidazole (92 mg) was further added thereto, and the mixture was stirred at 40° C. for 6 hours. The reaction solution was cooled and diluted with ethyl acetate and water. The organic layer was separated and successively washed with brine. After drying over magnesium sulfate, the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1) to give 1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-4-chloro-3-(5-(4-cyano-3-fluorophenyl)-2-thienylmethyl)benzene (158 mg) as colorless caramel. APCI-Mass m/Z 675/677 (M+NH4). (3) The above 1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-4-chloro-3-(5-(4-cyano-3-fluorophenyl)-2-thienylmethyl)benzene was treated in a manner similar to Example 106-(3) to give desired 1-(β-D-glucopyranosyl)-4-chloro-3-(5-(4-cyano-3-fluorophenyl)-2-thienylmethyl)benzene as pale yellow powder. APCI-Mass m/Z 507/509 (M+NH4).

Workup

  1. additionadded
  2. stirringthe mixture was stirred at 40° C. for 6 hours
  3. temperatureThe reaction solution was cooled
  4. customThe organic layer was separated
  5. washsuccessively washed with brine
  6. dry with materialAfter drying over magnesium sulfate
  7. customthe solvent was evaporated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1)

Sources & evidence

ORD record
ord-1dc76716755e4d18b5a4ebd8fe35a145
Source dataset
uspto-grants-2012_07
Patent number
US08222219B2

Reaction notes

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