Acetic Acid → HCID 68183184, compound

HRID 1615505Notes

Reaction equation

HRID 1615505 reaction equation
[O:1]=[C:2]([C:8]1[S:9][C:10]([C:13]2[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=2)=[CH:11][CH:12]=1)[CH2:3][C:4]([O:6][CH3:7])=[O:5].[Cl:19][C:20]1[CH:27]=[CH:26][C:23]([CH:24]=O)=[CH:22][CH:21]=1.N1CCCCC1.C1C=CC=CC=1.C(O)(=O)C>>[Cl:19][C:20]1[CH:27]=[CH:26][C:23](/[CH:24]=[C:3](/[C:2]([C:8]2[S:9][C:10]([C:13]3[CH:14]=[CH:15][N:16]=[CH:17][CH:18]=3)=[CH:11][CH:12]=2)=[O:1])\[C:4]([O:6][CH3:7])=[O:5])=[CH:22][CH:21]=1

Participants

6

Reactant 5

HCID 176Acetic AcidHCID 241BenzeneHCID 77264-ChlorobenzaldehydeHCID 8082PiperidineHCID 68183095HCID 68183095, compound

Product 1

HCID 68183184HCID 68183184, compoundYield 65.8%

Conditions

Temperature
92 °C

Procedure

To a 100 mL round bottom flask was added a solution of methyl 3-oxo-3-(5-pyridin-4-yl-2-thienyl)propanoate (0.150 g, 0.574 mmol), 4-chlorobenzaldehyde (0.097 g, 0.689 mmol) and piperidine (0.006 mL, 0.057 mmol) in anhydrous benzene (10.00 mL, 111.9 mmol). Acetic acid (0.023 mL, 0.401 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 dry loaded onto silica gel and then purified using ISCO (12 g cartridge, gradient hexanes to 100% EtOAc over 30 min) to afford the title compound (0.145 g, 63%) as a white solid. LC/MS (AA) ES+ 384, 386. 1H NMR (dmso-d6, 400 MHz): δ 8.66-8.65 (m, 2H), 8.00 (d, 1H), 7.84-7.75 (m, 4H), 7.47-7.46 (m, 4H), 3.76 (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. dry with materialThe crude material was dry
  6. custompurified
  7. customISCO (12 g cartridge, gradient hexanes to 100% EtOAc over 30 min)

Sources & evidence

ORD record
ord-c90b2154c26742e6b9ba1a3782dd64da
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

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