Acetic Acid → Ethyl 1-{[3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,3,4-thiadiazol-2-yl)-2-ethylphenyl]methyl}-4-piperidinecarboxylate

HRID 1942590Notes

Reaction equation

HRID 1942590 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[S:16][C:15]([C:17]3[C:18]([CH2:25][CH3:26])=[C:19]([CH:22]=[CH:23][CH:24]=3)[CH:20]=O)=[N:14][N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].[NH:27]1[CH2:32][CH2:31][CH:30]([C:33]([O:35][CH2:36][CH3:37])=[O:34])[CH2:29][CH2:28]1.C([O-])(=O)C.[Na+].CC(O)=O>CO>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[S:16][C:15]([C:17]3[C:18]([CH2:25][CH3:26])=[C:19]([CH2:20][N:27]4[CH2:32][CH2:31][CH:30]([C:33]([O:35][CH2:36][CH3:37])=[O:34])[CH2:29][CH2:28]4)[CH:22]=[CH:23][CH:24]=3)=[N:14][N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 70770Ethyl 4-piperidinecarboxylateHCID 517045Sodium AcetateHCID 584940093-(5-{3-Chloro-4-[(1-methylethyl)oxy]phenyl}-1,3,4-thiadiazol-2-yl)-2-ethylbenzaldehyde

Product 1

HCID 58494031Ethyl 1-{[3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,3,4-thiadiazol-2-yl)-2-ethylphenyl]methyl}-4-piperidinecarboxylateYield 100.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,3,4-thiadiazol-2-yl)-2-ethylbenzaldehyde (D11) (44 mg) and ethyl 4-piperidinecarboxylate (89 mg) in methanol (10.00 mL) stirred at room temperature was added sodium acetate (55 mg) and AcOH (0.033 mL). The reaction mixture was stirred at room temperature for 10 min. And the solvent was removed by evaporation. The residue was dissolved in dichloromethane (DCM) (10 mL), and sodium triacetoxyborohydride (72.3 mg) was added. Stirring continued for 2 h. Water was added to quench the reaction, and DCM was removed by evaporation. The mixture was extracted by EA for 3 times. The combined organic solution was washed by brine, dried over anhydrous Na2SO4. The dried solution was filtered and concentrated to afford ethyl 1-{[3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,3,4-thiadiazol-2-yl)-2-ethylphenyl]methyl}-4-piperidinecarboxylate (D12) (60.1 mg). MS (ES): C28H34ClN3O3S requires 527. found 528.2 (M+H+).

Workup

  1. customAnd the solvent was removed by evaporation
  2. dissolutionThe residue was dissolved in dichloromethane (DCM) (10 mL)
  3. additionsodium triacetoxyborohydride (72.3 mg) was added
  4. stirringStirring
  5. waitcontinued for 2 h
  6. additionWater was added
  7. customto quench
  8. customthe reaction, and DCM
  9. customwas removed by evaporation
  10. extractionThe mixture was extracted by EA for 3 times
  11. washThe combined organic solution was washed by brine
  12. dry with materialdried over anhydrous Na2SO4
  13. filtrationThe dried solution was filtered
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-31573f84a0e249e48512b4df5bdcdf0a
Source dataset
uspto-grants-2013_03
Patent number
US08389508B2

Reaction notes

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