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

HRID 1942586Notes

Reaction equation

HRID 1942586 reaction equation
[CH2:1]([C:3]1[C:10]([C:11]2[S:12][C:13]([C:16]3[CH:21]=[CH:20][C:19]([O:22][CH:23]([CH3:25])[CH3:24])=[C:18]([C:26]([F:29])([F:28])[F:27])[CH:17]=3)=[N:14][N:15]=2)=[CH:9][CH:8]=[CH:7][C:4]=1[CH:5]=O)[CH3:2].[NH:30]1[CH2:35][CH2:34][CH:33]([C:36]([O:38][CH2:39][CH3:40])=[O:37])[CH2:32][CH2:31]1.CC(O)=O>C(O)C>[CH2:1]([C:3]1[C:10]([C:11]2[S:12][C:13]([C:16]3[CH:21]=[CH:20][C:19]([O:22][CH:23]([CH3:24])[CH3:25])=[C:18]([C:26]([F:28])([F:29])[F:27])[CH:17]=3)=[N:14][N:15]=2)=[CH:9][CH:8]=[CH:7][C:4]=1[CH2:5][N:30]1[CH2:35][CH2:34][CH:33]([C:36]([O:38][CH2:39][CH3:40])=[O:37])[CH2:32][CH2:31]1)[CH3:2]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 70770Ethyl 4-piperidinecarboxylateHCID 866589982-Ethyl-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}benzaldehyde

Product 1

HCID 66981714Ethyl 1-[(2-ethyl-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}phenyl)methyl]-4-piperidinecarboxylateYield 99.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 2-ethyl-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}benzaldehyde (D6) (54 mg) and ethyl 4-piperidinecarboxylate (101 mg) in ethanol (10 mL) stirred at room temperature was added AcOH (0.037 mL). The reaction mixture was stirred at room temperature for 10 min. Then the solvent was removed by evaporation. To the residue was added dichloromethane (DCM) (10 mL) and sodium triacetoxyborohydride (82 mg). 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 phases were washed by brine, dried over anhydrous Na2SO4. The dried solution was filtered and concentrated to afford the crude product ethyl 1-[(2-ethyl-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}phenyl)methyl]-4-piperidinecarboxylate (D7) (72.1 mg). MS (ES): C29H34F3N3O3S requires 561. found 562.1 (M+H+).

Workup

  1. customThen the solvent was removed by evaporation
  2. additionTo the residue was added dichloromethane (DCM) (10 mL) and sodium triacetoxyborohydride (82 mg)
  3. stirringStirring
  4. waitcontinued for 2 h
  5. additionWater was added
  6. customto quench
  7. customthe reaction, and DCM
  8. customwas removed by evaporation
  9. extractionThe mixture was extracted by EA for 3 times
  10. washThe combined organic phases were washed by brine
  11. dry with materialdried over anhydrous Na2SO4
  12. filtrationThe dried solution was filtered
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-25e379eb5b8e45f18daed6c728ff9488
Source dataset
uspto-grants-2013_03
Patent number
US08389508B2

Reaction notes

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