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Trifluoroacetic acid → benzyl 3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenylcarbamate

HRID 1909456
Notes
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Reaction equation

HRID 1909456 reaction equation
[CH2:1]([O:8][C:9](=[O:22])[NH:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([C:17]2O[CH:19]=[N:20][N:21]=2)[CH:12]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:23]1([NH2:26])[CH2:25][CH2:24]1.FC(F)(F)C(O)=O>C(O)CCC>[CH2:1]([O:8][C:9](=[O:22])[NH:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([C:17]2[N:26]([CH:23]3[CH2:25][CH2:24]3)[CH:19]=[N:20][N:21]=2)[CH:12]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 69828CyclopropylamineHCID 66851996Benzyl 3-(1,3,4-oxadiazol-2-yl)phenylcarbamate

Product 1

HCID 66851731benzyl 3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenylcarbamateYield 31%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of (3-[1,3,4]Oxadiazol-2-yl-phenyl)-carbamic acid benzyl ester (200 mg, 0.68 mmol), cyclopropylamine (0.5 mL, 7.2 mmol), trifluoroacetic acid (0.05 mL, 0.65 mmol) in anhydrous 1-butanol (3 mL) was heated at 110° C. overnight in a sealed tube. The reaction mixture was cooled to room temperature and the solvent was removed. The residue was partitioned between ethyl acetate and saturated sodium bicarbonate solution, and the aqueous phase was extracted with ethyl acetate. Solvent was removed after drying with sodium sulfate and purified by silica gel chromatography (rf=0.26 in 20:1 ethyl acetate/methanol) to obtain [3-(4-Cyclopropyl-4H-[1,2,4]triazol-3-yl)-phenyl]-carbamic acid benzyl ester as a white powder (70 mg, 31%). M+1=335.1

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customthe solvent was removed
  3. customThe residue was partitioned between ethyl acetate and saturated sodium bicarbonate solution
  4. extractionthe aqueous phase was extracted with ethyl acetate
  5. customSolvent was removed
  6. dry with materialafter drying with sodium sulfate
  7. custompurified by silica gel chromatography (rf=0.26 in 20:1 ethyl acetate/methanol)

Sources & evidence

ORD record
ord-102fce979f1547a587e3faa78dd553c2
Source dataset
uspto-grants-2013_12
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08598360B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes