Acetic Acid → methyl (2Z)-2-[(5-bromo-2-thienyl)carbonyl]-3-(3,4-dichlorophenyl)acrylate

HRID 1615552Notes

Reaction equation

[Br:1][C:2]1[S:6][C:5]([C:7](=[O:13])[CH2:8][C:9]([O:11][CH3:12])=[O:10])=[CH:4][CH:3]=1.[Cl:14][C:15]1[CH:16]=[C:17]([CH:20]=[CH:21][C:22]=1[Cl:23])[CH:18]=O.N1CCCCC1.C(O)(=O)C>C1C=CC=CC=1>[Br:1][C:2]1[S:6][C:5]([C:7](/[C:8](=[CH:18]/[C:17]2[CH:20]=[CH:21][C:22]([Cl:23])=[C:15]([Cl:14])[CH:16]=2)/[C:9]([O:11][CH3:12])=[O:10])=[O:13])=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 110 °C

Procedure

To a 250 mL round bottom flask was added a solution of methyl 3-(5-bromo-2-thienyl)-3-oxopropanoate (25.11 g, 95.44 mmol), 3,4-dichloro-benzaldehyde (21.71 g, 124.1 mmol) and piperidine (0.944 mL, 9.54 mmol) in anhydrous benzene (682 mL). Acetic acid (3.80 mL, 66.8 mmol) was added and the reaction mixture was fitted with a Dean-Stark trap. The oil bath was heated to 110° C. and the reaction stirred at reflux for 18 hours. The reaction was cooled to ambient temperature and concentrated under reduced pressure. The crude material was dry loaded onto silica gel and purified by silica gel chromatography to afford the product as a yellow oil (36.7 g, 91.6%). LCMS: (AA) ES+: 421. 1H NMR (400 MHz, d6-DMSO) δ 7.83 (s, 1H), 7.53-7.45 (m, 1H), 7.34 (t, J=10.0 Hz, 1H), 7.24 (dd, J=8.4, 2.7 Hz, 2H), 7.03 (d, J=4.1 Hz, 1H), 3.81 (s, 3H).

Workup

customthe reaction mixture was fitted with a Dean-Stark trap
temperatureat reflux for 18 hours
temperatureThe reaction was cooled to ambient temperature
concentrationconcentrated under reduced pressure
dry with materialThe crude material was dry
custompurified by silica gel chromatography

Sources & evidence

ORD record: ord-a646758d6c2d4a8db5d1342cdf989969
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08765746B2

Reaction notes

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