1,2-Dichloroethane → trans-methyl 2-bromo-4-(4-chlorophenyl)-6-oxo-5,6-dihydro-4H-cyclopenta[b]thiophene-5-carboxylate

HRID 1615498Notes

Reaction equation

HRID 1615498 reaction equation
[Br:1][C:2]1[S:6][C:5]([C:7](/[C:9](=[CH:14]/[C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)/[C:10]([O:12][CH3:13])=[O:11])=[O:8])=[CH:4][CH:3]=1.ClCCCl.[Cl-].[Cl-].[Cl-].[Al+3]>>[Br:1][C:2]1[S:6][C:5]2[C:7](=[O:8])[C@@H:9]([C:10]([O:12][CH3:13])=[O:11])[C@H:14]([C:15]3[CH:16]=[CH:17][C:18]([Cl:21])=[CH:19][CH:20]=3)[C:4]=2[CH:3]=1

Participants

4

Reactant 3

HCID 111,2-DichloroethaneHCID 6451240Aluminum(III) ChlorideHCID 68183162(Z)-methyl 2-(5-bromothiophene-2-carbonyl)-3-(4-chlorophenyl)acrylate

Product 1

HCID 68191110trans-methyl 2-bromo-4-(4-chlorophenyl)-6-oxo-5,6-dihydro-4H-cyclopenta[b]thiophene-5-carboxylateYield 63.4%

Conditions

Temperature
80 °C

Procedure

To a 500 mL round bottom flask was added a solution of methyl (2Z)-2-[(5-bromo-2-thienyl)carbonyl]-3-(4-chlorophenyl)acrylate (6.26 g, 16.2 mmol), in 1,2-dichloroethane (210.0 mL, 2665.4 mmol). Aluminum trichloride (2.164 g, 16.23 mmol) was added and the reaction mixture was heated to 80° C. and allowed to stir 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 then purified using a ISCO (40 g cartridge, gradient hexanes to 30% EtOAc over 30 min) to afford the title compound (3.96 g, 60%) as a brown oil. LC/MS (AA) ES− 385, 387, 389. 1H NMR (dmso-d6, 400 MHz): δ 7.43-7.29 (m, 5H), 4.91 (d, 1H), 4.04 (d, 1H), 3.71 (s, 3H).

Workup

  1. temperatureThe reaction was cooled to ambient temperature
  2. concentrationconcentrated under reduced pressure
  3. dry with materialThe crude material was dry
  4. custompurified
  5. customa ISCO (40 g cartridge, gradient hexanes to 30% EtOAc over 30 min)

Sources & evidence

ORD record
ord-41a7ec992810431a8980d71c7ee0a409
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

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