4-Hydroxybenzaldehyde → HCID 86732650, compound

HRID 523333Notes

Reaction equation

HRID 523333 reaction equation
S(Cl)(Cl)=[O:2].[OH:5][C:6]1[CH:13]=[CH:12][C:9]([CH:10]=[O:11])=[CH:8][CH:7]=1.[N:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[C:20]([OH:26])(=[O:25])[CH2:21][C:22](O)=O.N1CCCC1.[C:32]1(C)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>CO.CN(C=O)C>[C:19]([CH2:18][CH2:17][CH2:16][CH2:15][O:5][C:6]1[CH:13]=[CH:12][C:9]([C:10]([O:2][C:32]2[CH:37]=[CH:36][C:35](/[CH:22]=[CH:21]/[C:20]([OH:26])=[O:25])=[CH:34][CH:33]=2)=[O:11])=[CH:8][CH:7]=1)#[N:14]

Participants

9

Reactant 6

HCID 1264-HydroxybenzaldehydeHCID 867Malonic AcidHCID 1049PyridineHCID 1140TolueneHCID 24386Thionyl ChlorideHCID 31268Pyrrolidine

Product 1

HCID 86732650HCID 86732650, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
75 °C

Procedure

17.9 g (82 mmol) of compound 40A is suspended in 56 mL of toluene and few drops of DMF are added. The suspension is heated up to 75° C. and 10.7 g (90 mmol) of thionylchloride are added. After 2 hours, the excess of thionylchloride is removed under pressure. The solution is cooled down to room temperature. 10.2 g (83 mmol) of 4-hydroxybenzaldehyde, 0.5 g (4 mmol) of 4-diaminopyridine and 28 g (355 mmol) of pyridine are added. After 3 hours, 14.5 g (140 mmol) of malonic acid and 3 g (42 mmol) of pyrrolidine are added. The reaction mixture is allowed to react at 80° C. for 30 min. Then, 16.8 mL of MeOH are incorporated and the suspension is cooled down and kept at 0° C. for 1 hour. The product is filtered off and suspended for 2 hours in a solution of 57 mL of MeOH, 11 mL of H2O and 7.5 g of a 25% HCl solution. The solid is filtered off and washed with MeOH and heptane. The product is crystallized in acetonitrile to give 23 g of (2E)-3-(4-{[4-(4-cyanobutoxy)benzoyl]oxy}phenyl)prop-2-enoic acid as a white powder.

Workup

  1. customthe excess of thionylchloride is removed under pressure
  2. temperatureThe solution is cooled down to room temperature
  3. waitAfter 3 hours
  4. customto react at 80° C. for 30 min
  5. temperaturethe suspension is cooled down
  6. waitkept at 0° C. for 1 hour
  7. filtrationThe product is filtered off
  8. waitsuspended for 2 hours in a solution of 57 mL of MeOH, 11 mL of H2O and 7.5 g of a 25% HCl solution
  9. filtrationThe solid is filtered off
  10. washwashed with MeOH and heptane
  11. customThe product is crystallized in acetonitrile

Sources & evidence

ORD record
ord-70b5c28c494a4e2db2abf3c01b58d391
Source dataset
uspto-grants-2016_05
Patent number
US09334366B2

Reaction notes

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