Sodium Acetate → Methyl 1-[(3-{5-[3-cyano-4-(2-methylpropyl)phenyl]-1,3,4-thiadiazol-2-yl}-2-ethylphenyl)methyl]-3-azetidinecarboxylate

HRID 1942605Notes

Reaction equation

HRID 1942605 reaction equation
[CH2:1]([C:3]1[C:8]([CH:9]=O)=[CH:7][CH:6]=[CH:5][C:4]=1[C:11]1[S:15][C:14]([C:16]2[CH:17]=[CH:18][C:19]([CH2:24][CH:25]([CH3:27])[CH3:26])=[C:20]([CH:23]=2)[C:21]#[N:22])=[N:13][N:12]=1)[CH3:2].[NH:28]1[CH2:31][CH:30]([C:32]([O:34][CH3:35])=[O:33])[CH2:29]1.C([O-])(=O)C.[Na+].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)C.ClCCl.O.CC(O)=O>[C:21]([C:20]1[CH:23]=[C:16]([C:14]2[S:15][C:11]([C:4]3[C:3]([CH2:1][CH3:2])=[C:8]([CH2:9][N:28]4[CH2:31][CH:30]([C:32]([O:34][CH3:35])=[O:33])[CH2:29]4)[CH:7]=[CH:6][CH:5]=3)=[N:12][N:13]=2)[CH:17]=[CH:18][C:19]=1[CH2:24][CH:25]([CH3:27])[CH3:26])#[N:22]

Participants

9

Reactant 4

HCID 517045Sodium AcetateHCID 5049666Sodium triacetoxyborohydrideHCID 20132751Methyl azetidine-3-carboxylateHCID 866590005-[5-(2-Ethyl-3-formylphenyl)-1,3,4-thiadiazol-2-yl]-2-(2-methylpropyl)benzonitrile

Product 1

HCID 66981738Methyl 1-[(3-{5-[3-cyano-4-(2-methylpropyl)phenyl]-1,3,4-thiadiazol-2-yl}-2-ethylphenyl)methyl]-3-azetidinecarboxylateYield 99.5%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-[5-(2-ethyl-3-formylphenyl)-1,3,4-thiadiazol-2-yl]-2-(2-methylpropyl)benzonitrile (D27) (31 mg) and methyl 3-azetidinecarboxylate (62.6 mg) in ethanol (10 mL) stirred at room temperature was added sodium acetate (33.9 mg) and AcOH (0.15 mL). The reaction mixture was stirred at room temperature for 10 min. The residue was dissolved in dichloromethane (DCM) (10 mL), sodium triacetoxyborohydride (52.5 mg) was added. Stirring continued for overnight. 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 methyl 1-[(3-{5-[3-cyano-4-(2-methylpropyl)phenyl]-1,3,4-thiadiazol-2-yl}-2-ethylphenyl)methyl]-3-azetidinecarboxylate (D29) (39 mg). MS (ES): C27H30N4O2S requires 474. found 475.2 (M+H+).

Workup

  1. stirringStirring
  2. waitcontinued for overnight
  3. customto quench
  4. customthe reaction, and DCM
  5. customwas removed by evaporation
  6. extractionThe mixture was extracted by EA for 3 times
  7. washThe combined organic solution was washed by brine
  8. dry with materialdried over anhydrous Na2SO4
  9. filtrationThe dried solution was filtered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-cd7e3bb12f0e495ab5628c3c5d647438
Source dataset
uspto-grants-2013_03
Patent number
US08389508B2

Reaction notes

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