Hydrochloric Acid → HCID 19358312, compound

HRID 377290Notes

Reaction equation

HRID 377290 reaction equation
[CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][CH:10]=[C:11]([C:18]4[CH:19]=[C:20]5[C:24](=[C:25]([O:27]C)[CH:26]=4)[CH2:23][N:22]([S:29]([C:32]4[CH:37]=[CH:36][C:35]([CH3:38])=[CH:34][CH:33]=4)(=[O:31])=[O:30])[CH2:21]5)[C:12]=3[O:14][CH:15]([F:17])[F:16])[C:7](=[O:39])[C:6]([C:40]([O:42]CC)=[O:41])=[CH:5]2)[CH2:3][CH2:2]1.B(Br)(Br)Br.[OH-].[Na+].Cl>C(Cl)Cl.C(O)C.O1CCOCC1.O.C(Cl)(Cl)Cl>[CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][CH:10]=[C:11]([C:18]4[CH:19]=[C:20]5[C:24](=[C:25]([OH:27])[CH:26]=4)[CH2:23][N:22]([S:29]([C:32]4[CH:33]=[CH:34][C:35]([CH3:38])=[CH:36][CH:37]=4)(=[O:30])=[O:31])[CH2:21]5)[C:12]=3[O:14][CH:15]([F:17])[F:16])[C:7](=[O:39])[C:6]([C:40]([OH:42])=[O:41])=[CH:5]2)[CH2:3][CH2:2]1

Participants

10

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 25134Boron tribromideHCID 19358326HCID 19358326, compound

Product 1

HCID 19358312HCID 19358312, compoundYield 46%

Reagents, catalysts & solvents 5

HCID 702EthanolSolventHCID 962WaterSolventHCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
-30 °C

Procedure

In 10 ml of methylene chloride was suspended 0.28 g of ethyl 1-cyclopropyl-8-difluoromethoxy-7-[7-methoxy-2-(p-toluenesulfonyl)isoindolin-5-yl]-1,4-dihydro-4-oxoquinoline-3-carboxylate, and the suspension was cooled to -30° C., after which 1.3 ml of 1.0 M solution of boron tribromide in methylene chloride was added dropwise thereto over a period of 5 minutes, and the resulting mixture was stirred at 0° C. for 2 hours. The reaction mixture was added to a mixed solvent of 10 ml of chloroform and 10 ml of water, and the organic layer was separated. The organic layer obtained was washed with water, dried over anhydrous magnesium sulfate, and then distilled under reduced pressure to remove the solvent. The resulting residue was purified by a column chromatography (eluent; chloroform:acetone=5:1) and the crystals thus obtained were suspended in 1.5 ml of ethanol and 1.5 ml of dioxane, after which 0.74 ml of a 1N aqueous sodium hydroxide solution was added thereto and the resulting mixture was stirred at 60° C. for 30 minutes. To the reaction mixture was added 0.74 ml of 1N hydrochloric acid and the crystals were collected by filtration to obtain 0.12 g of light-brown 1-cyclopropyl-8-difluoromethoxy-7-[7-hydroxy-2-(p-toluenesulfonyl)isoindolin-5-yl]-1,4-dihydro-4-oxoquinoline-3-carboxylic acid.

Workup

  1. customthe organic layer was separated
  2. customThe organic layer obtained
  3. washwas washed with water
  4. dry with materialdried over anhydrous magnesium sulfate
  5. distillationdistilled under reduced pressure
  6. customto remove the solvent
  7. customThe resulting residue was purified by a column chromatography (eluent; chloroform:acetone=5:1)
  8. customthe crystals thus obtained
  9. stirringthe resulting mixture was stirred at 60° C. for 30 minutes
  10. filtrationthe crystals were collected by filtration

Sources & evidence

ORD record
ord-6ec204f90e244609b8b0edade40ae4ea
Source dataset
uspto-grants-2000_02
Patent number
US06025370

Reaction notes

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