Water → 5-(3,5-Dibromo-4-hydroxyphenyl)-N-(3-(trifluoromethoxy)benzyl)-1,2,4-oxadiazole-3-carboxamide

HRID 222357Notes

Reaction equation

HRID 222357 reaction equation
C[Al](C)C.[F:5][C:6]([F:17])([F:16])[O:7][C:8]1[CH:9]=[C:10]([CH:13]=[CH:14][CH:15]=1)[CH2:11][NH2:12].[Br:18][C:19]1[CH:20]=[C:21]([C:27]2[O:31][N:30]=[C:29]([C:32](OCC)=[O:33])[N:28]=2)[CH:22]=[C:23]([Br:26])[C:24]=1[OH:25].O>CCCCCC.C(Cl)(Cl)Cl>[Br:26][C:23]1[CH:22]=[C:21]([C:27]2[O:31][N:30]=[C:29]([C:32]([NH:12][CH2:11][C:10]3[CH:13]=[CH:14][CH:15]=[C:8]([O:7][C:6]([F:16])([F:17])[F:5])[CH:9]=3)=[O:33])[N:28]=2)[CH:20]=[C:19]([Br:18])[C:24]=1[OH:25]

Participants

7

Reactant 4

HCID 962WaterHCID 1452643-(Trifluoromethoxy)benzylamineHCID 16682925TrimethylaluminumHCID 136139578Ethyl 5-(3,5-dibromo-4-hydroxyphenyl)-1,2,4-oxadiazole-3-carboxylate

Product 1

HCID 1358705485-(3,5-Dibromo-4-hydroxyphenyl)-N-(3-(trifluoromethoxy)benzyl)-1,2,4-oxadiazole-3-carboxamideYield 62%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolvent2×HCID 8058HexaneSolvent

Procedure

Trimethylaluminum (0.11 mL of a 2 N solution in hexane, 0.22 mmol) was added to a stirred solution of 3-(trifluoromethoxy)benzyl amine (42 mg, 0.22 mmol) in anhydrous chloroform (2 mL) under nitrogen and the resulting solution was stirred at room temperature for 20 minutes. Ethyl 5-(3,5-dibromo-4-hydroxyphenyl)-1,2,4-oxadiazole-3-carboxylate (78 mg, 0.2 mmol) was then added in one portion and the reaction was stirred at 50° C. for 5 h before standing at room temperature overnight. Water (2 mL) was added followed by more chloroform (3 mL), the organic phase was separated and evaporated to dryness to give a yellow oil. This was purified by preparative HPLC to give the title compound (66 mg, 62%) as a colourless solid. 1H NMR δ (ppm) (DMSO-d6): 4.58 (2H, d, J=6.20 Hz), 7.31 (1H, d, J=8.20 Hz), 7.39-7.47 (2H, m), 7.53 (1H, t, J=7.91 Hz), 8.20 (2H, s), 10.07 (1H, t, J=6.24 Hz). LCMS (10 cm_apci_formic) tR 4.14 min; m/z 534/536/538 [M−H]−.

Workup

  1. stirringthe reaction was stirred at 50° C. for 5 h
  2. waitbefore standing at room temperature overnight
  3. customthe organic phase was separated
  4. customevaporated to dryness
  5. customto give a yellow oil
  6. customThis was purified by preparative HPLC

Sources & evidence

ORD record
ord-038a0ef42b55490ab30378870f5cd2f2
Source dataset
uspto-grants-2012_06
Patent number
US08207205B2

Reaction notes

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