Potassium Carbonate → ethyl 5-(1-(4-fluorobenzyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-3-methylthiophene-2-carboxylate

HRID 2067577Notes

Reaction equation

[CH3:1][C:2]1[CH:6]=[C:5]([N:7]2[C:11](=[O:12])[NH:10][N:9]=[CH:8]2)[S:4][C:3]=1[C:13]([O:15][CH2:16][CH3:17])=[O:14].C(=O)([O-])[O-].[K+].[K+].[F:24][C:25]1[CH:32]=[CH:31][C:28]([CH2:29]Br)=[CH:27][CH:26]=1>CN(C)C=O>[F:24][C:25]1[CH:32]=[CH:31][C:28]([CH2:29][N:10]2[C:11](=[O:12])[N:7]([C:5]3[S:4][C:3]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[C:2]([CH3:1])[CH:6]=3)[CH:8]=[N:9]2)=[CH:27][CH:26]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of ethyl 3-methyl-5-(5-oxo-1H-1,2,4-triazol-4(5H)-yl)thiophene-2-carboxylate (0.15 g, 0.59 mmol), potassium carbonate (0.16 g, 1.19 mmol) and 4-fluorobenzyl bromide (0.11 mL, 0.90 mmol) in N,N-dimethylformamide (3 mL) was stirred at 80° C. for 18 h. The reaction mixture was allowed to cool to ambient temperature, then partitioned between ethyl acetate (75 mL) and water (35 mL). The organic layer was washed with brine (35 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluted with 0-40% ethyl acetate in hexanes to afford the title compound as a cream solid in 81% yield (0.17 g): 1H NMR (300 MHz, CDCl3) δ 7.72 (s, 1H), 7.42-7.36 (m, 2H), 7.08-7.01 (m, 2H), 6.93 (s, 1H), 4.98 (s, 2H), 4.32 (q, J=7.1 Hz, 2H), 2.54 (s, 3H), 1.36 (t, J=7.1 Hz, 3H); MS (ES+) m/z 362.2 (M+1).

Workup

temperatureto cool to ambient temperature
custompartitioned between ethyl acetate (75 mL) and water (35 mL)
washThe organic layer was washed with brine (35 mL)
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified by column chromatography
washeluted with 0-40% ethyl acetate in hexanes

Sources & evidence

ORD record: ord-10a4cb15727a4a1c82b100838a53662e
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08293768B2

Reaction notes

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