1-Hydroxybenzotriazole → N-(4-(3-bromophenyl)-3-hydroxybutan-2-yl)-3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazole-5-carboxamide

HRID 517535Notes

Reaction equation

HRID 517535 reaction equation
[F:1][C:2]([F:19])([F:18])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[N:14]=[C:13]([C:15]([O-:17])=O)[O:12][N:11]=2)=[CH:6][CH:5]=1.[Na+].CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.[NH2:52][CH:53]([CH3:64])[CH:54]([OH:63])[CH2:55][C:56]1[CH:61]=[CH:60][CH:59]=[C:58]([Br:62])[CH:57]=1>C(Cl)Cl>[Br:62][C:58]1[CH:57]=[C:56]([CH2:55][CH:54]([OH:63])[CH:53]([NH:52][C:15]([C:13]2[O:12][N:11]=[C:10]([C:7]3[CH:6]=[CH:5][C:4]([O:3][C:2]([F:1])([F:19])[F:18])=[CH:9][CH:8]=3)[N:14]=2)=[O:17])[CH3:64])[CH:61]=[CH:60][CH:59]=1

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 823860203-Amino-1-(3-bromophenyl)butan-2-olHCID 86711476Sodium 3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazole-5-carboxylate

Product 1

HCID 86711478N-(4-(3-bromophenyl)-3-hydroxybutan-2-yl)-3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazole-5-carboxamideYield 41.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of sodium 3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazole-5-carboxylate (500 mg, 1.7 mmol) in DCM (15 mL), DIEA (436 mg, 3.4 mmol), EDC.HCl (496 mg, 2.6 mmol), HOBT (351 mg, 2.6 mmol) and 3-amino-1-(3-bromophenyl)butan-2-ol (500 mg, 2.0 mmol) were added in sequence. The mixture was stirred at RT for 2 h, heated at 40 overnight, cooled to RT, quenched by the addition of H2O (50 mL), and extracted with DCM (50 mL×3). The combined organic layers were washed with H2O (10 mL) and brine (10 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Petroleum ether:EtOAc=5:1) to afford N-(4-(3-bromophenyl)-3-hydroxybutan-2-yl)-3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazole-5-carboxamide (350 mg, 41%) as a white solid. MS (ES+) C20H13BrF3N3O3 requires: 499, 501 found: 500 [M+H]+, 502 [M+2+H]+(1:1).

Workup

  1. temperatureheated at 40 overnight
  2. temperaturecooled to RT
  3. customquenched by the addition of H2O (50 mL)
  4. extractionextracted with DCM (50 mL×3)
  5. washThe combined organic layers were washed with H2O (10 mL) and brine (10 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (Petroleum ether:EtOAc=5:1)

Sources & evidence

ORD record
ord-4872cf27d17549d8b32050319ac8b826
Source dataset
uspto-grants-2015_08
Patent number
US09115120B2

Reaction notes

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