Dimethylformamide → 3-(3-Bromo-5-iodo-2-thienyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazole

HRID 2401732Notes

Reaction equation

HRID 2401732 reaction equation
[Br:1][C:2]1[CH:6]=[C:5]([I:7])[S:4][C:3]=1[C:8]1[NH:12][CH:11]=[N:10][N:9]=1.C(N(CC)C(C)C)(C)C.CN(C)C=O.[CH3:27][Si:28]([CH3:35])([CH3:34])[CH2:29][CH2:30][O:31][CH2:32]Cl>CCOC(C)=O.O>[Br:1][C:2]1[CH:6]=[C:5]([I:7])[S:4][C:3]=1[C:8]1[N:12]=[CH:11][N:10]([CH2:32][O:31][CH2:30][CH2:29][Si:28]([CH3:35])([CH3:34])[CH3:27])[N:9]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 178419408HCID 178419408, compound

Product 1

HCID 667494683-(3-Bromo-5-iodo-2-thienyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazole

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

Into a solution of 3-(3-bromo-5-iodo-2-thienyl)-4H-1,2,4-triazole (500.0 mg, 1.40 mmol), N,N-dimethylaminopyridine (17.2 mg, 0.140 mmol) and N,N-diisopropylethylamine (0.32 mL, 1.83 mmol) in N,N-dimethylformamide (17.0 mL, 220 mmol) was added [β-(Trimethylsilyl)ethoxy]methyl chloride (0.270 mL, 1.55 mmol) was added and the solution was stirred for 2 h at rt. Water (5.0 mL) and EtOAc (5 mL) were added, the organic layer was separated, washed with brine, dried over MgSO4, filtered, concentrated and the obtained residue was purified by column chromatography (SiO2, elution with 0-30% EtOAc in hexane) to give the title compound as a yellowish oil (653 mg, (87% major isomer, 13% minor isomer) LCMS: (FA) ES+, 486, 488. (major isomer) 1H NMR (400 MHz, d6-DMSO) δ: 8.81 (s, 1H), 7.45 (s, 1H), 5.540-5.545 (s, br, 2H), 3.62-3.66 (m, 2H), 0.840-0.880 (m, 2H), −0.05 (s, 9H). LCMS: (FA) ES+ , 486, 488. (minor isomer) 1H NMR (400 MHz, d6-DMSO) δ: 8.215 (s, 1H), 7.615 (s, 1H), 5.48 (s, br, 2H), 3.44-3.50 (m, 2H), 0.75-0.80 (m, 2H), −0.08 (s, 9H).

Workup

  1. additionwas added
  2. customthe organic layer was separated
  3. washwashed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customthe obtained residue was purified by column chromatography (SiO2, elution with 0-30% EtOAc in hexane)

Sources & evidence

ORD record
ord-f084ddbfff324f84b00d31f7d5c33587
Source dataset
uspto-grants-2014_08
Patent number
US08796268B2

Reaction notes

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