Acetic Acid → (Z)-methyl 2-(5-bromothiophene-2-carbonyl)-3-(4-chlorophenyl)acrylate

HRID 1615497Notes

Reaction equation

HRID 1615497 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:22]=[CH:21][C:18]([CH:19]=O)=[CH:17][CH:16]=1.N1CCCCC1.C1C=CC=CC=1.C(O)(=O)C>>[Br:1][C:2]1[S:6][C:5]([C:7](/[C:8](=[CH:19]/[C:18]2[CH:21]=[CH:22][C:15]([Cl:14])=[CH:16][CH:17]=2)/[C:9]([O:11][CH3:12])=[O:10])=[O:13])=[CH:4][CH:3]=1

Participants

6

Reactant 5

HCID 176Acetic AcidHCID 241BenzeneHCID 77264-ChlorobenzaldehydeHCID 8082PiperidineHCID 14456695Methyl 3-(5-bromothiophen-2-yl)-3-oxopropanoate

Product 1

HCID 68183162(Z)-methyl 2-(5-bromothiophene-2-carbonyl)-3-(4-chlorophenyl)acrylateYield 97%

Conditions

Temperature
92 °C

Procedure

To a 500 mL round bottom flask was added a solution of methyl 3-(5-bromo-2-thienyl)-3-oxopropanoate (4.402 g, 16.73 mmol), 4-chlorobenzaldehyde (2.822 g, 20.08 mmol) and piperidine (0.165 mL, 1.673 mmol) in anhydrous benzene (200.0 mL, 2238 mmol). Acetic acid (0.665 mL, 11.712 mmol) was added and the reaction mixture was fitted with a Dean-Stark trap and the bath was heated to 92° C. and allowed to reflux for 18 hours. The reaction was cooled to ambient temperature and concentrated under reduced pressure. The crude material was split in half and dry loaded onto silica gel and then purified using a ISCO (40 g cartridge, gradient hexanes to 40% EtOAc over 30 min) to afford the title compound (6.26 g, 92%) as a yellow solid. LC/MS (AA) ES− 385, 387, 389(dmso-d6, 400 MHz): δ 7.89 (s, 1H), 7.34-7.24 (m, 5H), 7.00 (d, 1H), 3.71 (s, 3H).

Workup

  1. customthe reaction mixture was fitted with a Dean-Stark trap
  2. temperatureto reflux for 18 hours
  3. temperatureThe reaction was cooled to ambient temperature
  4. concentrationconcentrated under reduced pressure
  5. customThe crude material was split in half
  6. customdry
  7. custompurified
  8. customa ISCO (40 g cartridge, gradient hexanes to 40% EtOAc over 30 min)

Sources & evidence

ORD record
ord-c187639940ab4b3eaffb20d9058c5565
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

Loading…