Hydrochloric Acid → HCID 21997539, compound

HRID 1977278Notes

Reaction equation

HRID 1977278 reaction equation
OC1C=CC(C2SC([C:13]3C=C[C:16]([C:17]([O:19][CH3:20])=O)=[CH:15][CH:14]=3)=NN=2)=CC=1.[OH:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]2[S:34][C:33]([C:35]3[CH:43]=[CH:42][C:38]([C:39]([OH:41])=[O:40])=[CH:37][CH:36]=3)=[N:32][N:31]=2)=[CH:26][CH:25]=1.C(=O)([O-])[O-].[K+].[K+].BrCCCCCBr.Cl.C[O-].[Na+]>O1CCCC1.O.CO.CN(C)C=O>[CH3:20][O:19][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][O:23][C:24]1[CH:25]=[CH:26][C:27]([C:30]2[S:34][C:33]([C:35]3[CH:43]=[CH:42][C:38]([C:39]([OH:41])=[O:40])=[CH:37][CH:36]=3)=[N:32][N:31]=2)=[CH:28][CH:29]=1

Participants

11

Reactant 6

HCID 313Hydrochloric Acid2×HCID 81001,5-DibromopentaneHCID 11430Potassium CarbonateHCID 10942334Sodium Methoxide2×HCID 135815284HCID 135815284, compoundHCID 135815286HCID 135815286, compound

Product 1

HCID 21997539HCID 21997539, compound

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

To a suspension of a mixture of methyl 4-[5-(4-hydroxyphenyl)-1,3,4-thiadiazol-2-yl]benzoate and 4-[5-(4-hydroxyphenyl)-1,3,4-thiadiazol-2-yl]benzoic acid (3.12 g), potassium carbonate (22.07 g) and N,N-dimethylformamide (15 ml) was added 1,5-dibromopentane (15 ml) and the mixture was stirred at 100° C. (bath temperature) for 5 hours. The resulting mixture was neutralized by 0.1N hydrochloric acid and extracted with dichloromethane. The organic layer was washed with brine and dried over magnesium sulfate. The solvents were removed under reduced pressure and the residue was triturated with n-hexane. The solid was collected by filtration and dried to give a crude powder (3.71 g). To the crude powder (2.11 g) was added methanol (100 ml) and sodium methoxide (28% in methanol) (10 ml), and refluxed for 2 hours. Then to the reaction mixture was added sodium methoxide (28% in methanol) (5 ml) and refluxed for 1.5 hours. After cooling, the reaction mixture was added to water and tetrahydrofuran, stirred overnight and adjusted to pH 2 with 4N hydrochloric acid. The resulting precipitate was collected by filtration, washed with acetonitrile and dried under reduced pressure to give 4-[5-[4-(5-methoxy-n-pentyloxy) phenyl]-1,3,4-thiadiazol-2-yl]benzoic acid (1.34 g).

Workup

  1. extractionextracted with dichloromethane
  2. washThe organic layer was washed with brine
  3. dry with materialdried over magnesium sulfate
  4. customThe solvents were removed under reduced pressure
  5. customthe residue was triturated with n-hexane
  6. filtrationThe solid was collected by filtration
  7. customdried
  8. customto give a crude powder (3.71 g)
  9. temperaturerefluxed for 2 hours
  10. temperaturerefluxed for 1.5 hours
  11. temperatureAfter cooling
  12. stirringstirred overnight
  13. filtrationThe resulting precipitate was collected by filtration
  14. washwashed with acetonitrile
  15. customdried under reduced pressure

Sources & evidence

ORD record
ord-635e51de187c4418aab8c4fb804b3967
Source dataset
uspto-grants-2001_05
Patent number
US06232290B1

Reaction notes

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