Hydrochloric Acid → HCID 57787244, compound

HRID 2426779Notes

Reaction equation

HRID 2426779 reaction equation
Cl[C:2]([N:4]=[C:5]=[O:6])=[O:3].[OH:7][NH:8][CH2:9][C:10]1[CH:40]=[CH:39][C:13]([O:14][CH2:15][C:16]2[CH:17]=[C:18]([C:22]3[C:27]([CH3:28])=[CH:26][C:25]([O:29][CH2:30][C:31]4([OH:37])[CH2:36][CH2:35][S:34][CH2:33][CH2:32]4)=[CH:24][C:23]=3[CH3:38])[CH:19]=[CH:20][CH:21]=2)=[CH:12][CH:11]=1.Cl.C[O-].[Na+:44]>O.CO.C1COCC1>[OH:37][C:31]1([CH2:30][O:29][C:25]2[CH:26]=[C:27]([CH3:28])[C:22]([C:18]3[CH:19]=[CH:20][CH:21]=[C:16]([CH2:15][O:14][C:13]4[CH:12]=[CH:11][C:10]([CH2:9][N:8]5[C:5](=[O:6])[N-:4][C:2](=[O:3])[O:7]5)=[CH:40][CH:39]=4)[CH:17]=3)=[C:23]([CH3:38])[CH:24]=2)[CH2:32][CH2:33][S:34][CH2:35][CH2:36]1.[Na+:44]

Participants

8

Reactant 4

HCID 313Hydrochloric Acid2×HCID 119708Isocyanatocarbonyl chlorideHCID 10942334Sodium Methoxide2×HCID 57787237HCID 57787237, compound

Product 1

HCID 57787244HCID 57787244, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

Chlorocarbonyl isocyanate (0.14 ml) was dropwise added, under cooling on an ice-methanol bath, to a THF (15 ml) solution of 4-({[3′-({4-[(hydroxyamino)methyl]phenoxy}methyl)-2,6-dimethylbiphenyl-4-yl]oxy}methyl)tetrahydro-2H-thiopyran-4-ol (792 mg), followed by temperature rising to room temperature and subsequent 1 hour of stirring. A 1 M hydrochloric acid (40 ml) was added to the reaction mixture, followed by extraction with chloroform. The organic layer was dried over anhydrous magnesium sulfate and then the solvent was evaporated under a reduced pressure. By purifying the resulting residue by silica gel column chromatography (chloroform-methanol), a colorless foamy substance (777 mg) was obtained. Sodium methoxide (50 mg) was added to a methanol (10 ml) solution of the resulting foamy substance (116 mg), followed by stirring at room temperature for 30 minutes. Thereafter, sodium methoxide (200 mg) was added to the reaction mixture, followed by stirring at room temperature for 1 hour. The reaction mixture was warmed up to 60° C., stirred for 2 hours and then spontaneously cooled to room temperature. 1 M Hydrochloric acid (10 ml) and water (20 ml) were added to the reaction mixture, followed by extraction with chloroform. The organic layer was dried over anhydrous magnesium sulfate and then the solvent was evaporated under a reduced pressure. The resulting residue was dissolved in methanol (5 ml)-THF (10 ml), and a 1 M sodium hydroxide aqueous solution (0.20 ml) was added, followed by concentration under a reduced pressure. By washing the resulting residue with isopropanol-diethyl ether, sodium 2-[4-({4′-[(4-hydroxytetrahydro-2H-thiopyran-4-yl)methoxy]-2′,6′-dimethylbiphenyl-3-yl}methoxy)benzyl]-3,5-dioxo-1,2,4-oxadiazolidin-4-ide (80 mg) was obtained as a pale yellow solid.

Workup

  1. extractionfollowed by extraction with chloroform
  2. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  3. customthe solvent was evaporated under a reduced pressure
  4. customBy purifying the resulting residue by silica gel column chromatography (chloroform-methanol)
  5. customa colorless foamy substance (777 mg) was obtained
  6. stirringby stirring at room temperature for 30 minutes
  7. stirringby stirring at room temperature for 1 hour
  8. stirringstirred for 2 hours
  9. temperaturespontaneously cooled to room temperature
  10. extractionfollowed by extraction with chloroform
  11. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  12. customthe solvent was evaporated under a reduced pressure
  13. dissolutionThe resulting residue was dissolved in methanol (5 ml)-THF (10 ml)
  14. additiona 1 M sodium hydroxide aqueous solution (0.20 ml) was added
  15. concentrationfollowed by concentration under a reduced pressure
  16. washBy washing the resulting residue with isopropanol-diethyl ether

Sources & evidence

ORD record
ord-d256b08cbac54367ad8cb3621472bc62
Source dataset
uspto-grants-2011_06
Patent number
US07968552B2

Reaction notes

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