Acetic Acid → 2-bromo-1-[3-methyl-1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]ethan-1-one

HRID 1629128Notes

Reaction equation

C([O:3][C:4]([C:6]1[N:7]([CH:12]([CH3:14])[CH3:13])[N:8]=[C:9]([CH3:11])[N:10]=1)=O)C.[Br:15][CH2:16]Br.C[Li].C(O)(=O)C>C1COCC1.O>[Br:15][CH2:16][C:4]([C:6]1[N:7]([CH:12]([CH3:14])[CH3:13])[N:8]=[C:9]([CH3:11])[N:10]=1)=[O:3]

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 2-isopropyl-5-methyl-2H-[1,2,4]triazole-3-carboxylic acid ethyl ester (12.09 g, 61.3 mmol) and dibromomethane (8.63 mL, 122.6 mmol) in THF (500 mL) at −78° C. was added methyllithium (40.9 mL, 122.6 mmol, 3M solution in diethoxymethane) dropwise. The reaction mixture was stirred at −78° C. for 15 min. Acetic acid (3 mL) was added and the reaction mixture allowed to warm to RT. The reaction mixture was diluted with water and extracted with ethyl acetate (3×30 mL). The combined organic extracts were washed with brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0-100% ethyl acetate in cyclohexane) to give 2-Bromo-1-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-ethanone as a colourless oil which crystallised on standing (11.26 g, 75%). 1H NMR 400 MHz (CDCl3) δ: 5.41 (1H, sept, J=6.6 Hz), 4.67 (2H, s), 2.44 (3H, s), 1.49 (6H, d, J=6.6 Hz)

Workup

temperatureto warm to RT
extractionextracted with ethyl acetate (3×30 mL)
washThe combined organic extracts were washed with brine
dry with materialdried (MgSO4)
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-6b3d00ba015b43da9dbff7e02d6ef80f
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08785626B2

Reaction notes

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