Sodium Acetate → Methyl 1-[2-(2-ethyl-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}phenyl)ethyl]-3-azetidinecarboxylate

HRID 1942598Notes

Reaction equation

HRID 1942598 reaction equation
[CH2:1]([C:3]1[C:8]([C:9]2[S:10][C:11]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH:21]([CH3:23])[CH3:22])=[C:16]([C:24]([F:27])([F:26])[F:25])[CH:15]=3)=[N:12][N:13]=2)=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:28][CH:29]=O)[CH3:2].[NH:31]1[CH2:34][CH:33]([C:35]([O:37][CH3:38])=[O:36])[CH2:32]1.C([O-])(=O)C.[Na+].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO.ClCCl.O.CC(O)=O>[CH2:1]([C:3]1[C:8]([C:9]2[S:10][C:11]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH:21]([CH3:22])[CH3:23])=[C:16]([C:24]([F:26])([F:27])[F:25])[CH:15]=3)=[N:12][N:13]=2)=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:28][CH2:29][N:31]1[CH2:34][CH:33]([C:35]([O:37][CH3:38])=[O:36])[CH2:32]1)[CH3:2]

Participants

9

Reactant 4

HCID 517045Sodium AcetateHCID 5049666Sodium triacetoxyborohydrideHCID 20132751Methyl azetidine-3-carboxylateHCID 86658999(2-Ethyl-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}phenyl)acetaldehyde

Product 1

HCID 66981783Methyl 1-[2-(2-ethyl-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}phenyl)ethyl]-3-azetidinecarboxylateYield 50.9%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (2-ethyl-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}phenyl)acetaldehyde (D19) (40 mg) and methyl 3-azetidinecarboxylate (53.0 mg) in methanol (10 mL) stirred at room temperature was added sodium acetate (37.8 mg) and AcOH (0.026 mL). The reaction mixture was stirred at room temperature for 10 min. The residue was dissolved in dichloromethane (DCM) (10 mL), and sodium triacetoxyborohydride (58.5 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-[2-(2-ethyl-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}phenyl)ethyl]-3-azetidinecarboxylate (D20) (25 mg), which was used for the next without further purification. MS (ES): C27H30F3N3O3S requires 533. found 534.2 (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-32a4a460bf944b36b259e95c5c6573b6
Source dataset
uspto-grants-2013_03
Patent number
US08389508B2

Reaction notes

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