4-Toluenesulfonyl chloride → 4-{2-Chloro-4-[(5-chloro-6-methoxypyridin-2-yl)carbonyl]phenoxy}butyl 4-methylbenzenesulfonate

HRID 70501Notes

Reaction equation

HRID 70501 reaction equation
C(N(CC)CC)C.Cl.CN(C)C.[CH3:13][C:14]1[CH:19]=[CH:18][C:17]([S:20](Cl)(=[O:22])=[O:21])=[CH:16][CH:15]=1.[Cl:24][C:25]1[CH:26]=[C:27]([C:37]([C:39]2[CH:44]=[CH:43][C:42]([Cl:45])=[C:41]([O:46][CH3:47])[N:40]=2)=[O:38])[CH:28]=[CH:29][C:30]=1[O:31][CH2:32][CH2:33][CH2:34][CH2:35][OH:36]>C(Cl)(Cl)Cl.O>[CH3:13][C:14]1[CH:19]=[CH:18][C:17]([S:20]([O:36][CH2:35][CH2:34][CH2:33][CH2:32][O:31][C:30]2[CH:29]=[CH:28][C:27]([C:37]([C:39]3[CH:44]=[CH:43][C:42]([Cl:45])=[C:41]([O:46][CH3:47])[N:40]=3)=[O:38])=[CH:26][C:25]=2[Cl:24])(=[O:22])=[O:21])=[CH:16][CH:15]=1

Participants

7

Reactant 4

HCID 73974-Toluenesulfonyl chloride2×HCID 8471Triethylamine2×HCID 10313079Trimethylamine HydrochlorideHCID 67398017[3-Chloro-4-(4-hydroxybutoxy)phenyl](5-chloro-6-methoxypyridin-2-yl)methanone

Product 1

HCID 584527454-{2-Chloro-4-[(5-chloro-6-methoxypyridin-2-yl)carbonyl]phenoxy}butyl 4-methylbenzenesulfonateYield 70%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6212ChloroformSolvent

Procedure

Triethylamine (830 μL), trimethylamine hydrochloride (188 mg) and 4-methylbenzenesulfonyl chloride (555 mg) were sequentially added to a solution of [3-chloro-4-(4-hydroxybutoxy)phenyl](5-chloro-6-methoxypyridin-2-yl)methanone obtained in Reference Example 1-34(1) (360 mg) in chloroform (8 mL) under ice-cooling, and the mixture was stirred at room temperature for 4.5 hours. Triethylamine (150 μL) and 4-methylbenzenesulfonyl chloride (185 mg) were sequentially added under ice-cooling, and the mixture was stirred at room temperature for further 1.5 hours. Water was added to the reaction solution, followed by extraction with chloroform. The organic layer was dried over anhydrous magnesium sulfate and filtered. The solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=3:1) to give the title compound (357 mg, 70%).

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. stirringthe mixture was stirred at room temperature for further 1.5 hours
  4. extractionfollowed by extraction with chloroform
  5. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. customThe solvent was then evaporated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=3:1)

Sources & evidence

ORD record
ord-efa0e8f8f6ed4ae795b91739cdb6e267
Source dataset
uspto-grants-2014_09
Patent number
US08822503B2

Reaction notes

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