Dimethyl Sulfoxide → 2-bromo-4-(4-chlorophenyl)-4H-cyclopenta[b]thiophen-6(5H)-one

HRID 1615499Notes

Reaction equation

HRID 1615499 reaction equation
[Br:1][C:2]1[S:6][C:5]2[C:7](=[O:21])[CH:8](C(OC)=O)[CH:9]([C:10]3[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=3)[C:4]=2[CH:3]=1.CS(C)=O.O>>[Br:1][C:2]1[S:6][C:5]2[C:7](=[O:21])[CH2:8][CH:9]([C:10]3[CH:11]=[CH:12][C:13]([Cl:16])=[CH:14][CH:15]=3)[C:4]=2[CH:3]=1

Participants

4

Reactant 3

HCID 679Dimethyl SulfoxideHCID 962WaterHCID 68183216methyl 2-bromo-4-(4-chlorophenyl)-6-oxo-5,6-dihydro-4H-cyclopenta[b]thiophene-5-carboxylate

Product 1

HCID 681829442-bromo-4-(4-chlorophenyl)-4H-cyclopenta[b]thiophen-6(5H)-oneYield 86.2%

Conditions

Temperature
150 °C

Procedure

To a 500 mL round bottom flask was added a solution of methyl 2-bromo-4-(4-chlorophenyl)-6-oxo-5,6-dihydro-4H-cyclopenta[b]thiophene-5-carboxylate (3.96 g, 10.3 mmol) in dimethyl sulfoxide (88.393 mL, 1245.6 mmol). Water (4.420 mL, 245.3 mmol) was added and the reaction mixture was heated to 150° C. and allowed to stir for 3 hours. The reaction was cooled to ambient temperature and quenched by the addition of a saturated aqueous solution of sodium bicarbonate (500 mL) and extracted with EtOAc (300 mL×3). The combined organic layers were dried over anhydrous Na2SO4, filtered 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 100% EtOAc over 30 min) to afford the title compound (2.91 g, 82%) as a brown oil. LC/MS (AA) ES− 327, 329, 331. 1H NMR (dmso-d6, 400 MHz): δ 7.40-7.38 (m, 2H), 7.31 (s, 1H). 7.24-7.22 (m, 2H), 4.67 (dd, 1H), 3.40 (dd, 1H), 2.72 (dd, 1H).

Workup

  1. temperatureThe reaction was cooled to ambient temperature
  2. customquenched by the addition of a saturated aqueous solution of sodium bicarbonate (500 mL)
  3. extractionextracted with EtOAc (300 mL×3)
  4. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. dry with materialThe crude material was dry
  8. custompurified
  9. customa ISCO (40 g cartridge, gradient hexanes to 100% EtOAc over 30 min)

Sources & evidence

ORD record
ord-66825eaa6e9f423a999d0c978693045e
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

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