Ethyl 4-bromo-3-methylthiophene-2-carboxylate → 1034981-21-9

HRID 2381793Notes

Reaction equation

Br[C:2]1[S:6][C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[C:4]([CH3:12])[CH:3]=1.BrC1C(C)=C(C(OCC)=O)SC=1.[Cu](C#N)[C:26]#[N:27]>CN(C)C=O>[C:26]([C:2]1[S:6][C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[C:4]([CH3:12])[CH:3]=1)#[N:27]

Participants

Conditions

Temperature: 150 °C

Procedure

A mixture of ethyl 5-bromo-3-methylthiophene-2-carboxylate and ethyl 4-bromo-3-methylthiophene-2-carboxylate (˜1:4) (7.12 g, 28.60 mmol) and copper cyanide (7.68 g, 85.79 mmol) in anhydrous N,N-dimethylformamide (50 mL) was stirred under nitrogen atmosphere at 150° C. for 5 h. The mixture was allowed to cool to ambient temperature, and then partitioned between ethyl acetate (200 mL) and 14% aqueous ammonium hydroxide (200 mL). The organic layer was washed with 14% aqueous ammonium hydroxide (2×100 mL) and brine (100 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The two regioisomers were separated by column chromatography eluted with 2% ethyl acetate in hexanes to afford the title compound as a colorless solid (0.42 g, 38%): 1H NMR (300 MHz, CDCl3) δ 7.39 (s, 1H), 4.36 (q, J=7.1 Hz, 2H), 2.55 (s, 3H), 1.38 (t, J=7.1 Hz, 3H); MS (ES+) m/z 196.1 (M+1).

Workup

temperatureto cool to ambient temperature
custompartitioned between ethyl acetate (200 mL) and 14% aqueous ammonium hydroxide (200 mL)
washThe organic layer was washed with 14% aqueous ammonium hydroxide (2×100 mL) and brine (100 mL)
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customThe two regioisomers were separated by column chromatography
washeluted with 2% ethyl acetate in hexanes

Sources & evidence

ORD record: ord-b9a57d55f069498ca14a4e94cd8c10c3
Source dataset: uspto-grants-2012_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08258160B2

Reaction notes

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