4-Toluenesulfonyl chloride → YHO-13351 free base

HRID 2366444

Reaction equation

HRID 2366444 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5](/[C:11](=[CH:14]/[C:15]2[S:16][C:17]([N:20]3[CH2:25][CH2:24][CH:23]([OH:26])[CH2:22][CH2:21]3)=[CH:18][CH:19]=2)/[C:12]#[N:13])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[Na+].[CH2:28]([N:30]([CH2:35][CH3:36])[CH2:31][C:32]([O-])=[O:33])[CH3:29].C1(C)C=CC(S(Cl)(=O)=O)=CC=1>N1C=CC=CC=1>[CH2:28]([N:30]([CH2:31][C:32]([O:26][CH:23]1[CH2:22][CH2:21][N:20]([C:17]2[S:16][C:15](/[CH:14]=[C:11](\[C:12]#[N:13])/[C:5]3[CH:6]=[CH:7][C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=3)=[CH:19][CH:18]=2)[CH2:25][CH2:24]1)=[O:33])[CH2:35][CH3:36])[CH3:29]

Participants

5

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 16757522(Z)-2-(3,4-dimethoxyphenyl)-3-(5-(4-hydroxypiperidin-1-yl)thiophen-2-yl)acrylonitrileHCID 23670834Glycine, N,N-diethyl-, sodium salt (1:1)

Product 1

HCID 11964785YHO-13351 free baseYield 75%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

Compound 6 (3.70 g) was dissolved in pyridine (100 mL), and N,N-diethylglycin sodium salt (7.66 g) was added to the solution, followed by stirring at room temperature for 1 hour. Subsequently, p-toluenesulfonyl chloride (9.43 g) was added to the mixture, followed by stirring under reflux for 12 hours. After completion of reaction, the solvent was evaporated under reduced pressure. Chloroform (1,000 mL) was added to the residue, and the mixture was washed with water three times. The pH of the aqueous layer was checked by use of a pH testpaper, and adjusted to 4 to 5 with 1N aqueous hydrochloric acid. The organic layer was dried over sodium sulfate anhydrate, and the solvent was evaporated to dryness. The residue was purified by silica gel column chromatography (CHCl3-Hexane), to thereby yield the target product (yield: 3.62 g, 75%).

Workup

  1. stirringby stirring
  2. temperatureunder reflux for 12 hours
  3. customAfter completion of reaction
  4. customthe solvent was evaporated under reduced pressure
  5. additionChloroform (1,000 mL) was added to the residue
  6. washthe mixture was washed with water three times
  7. dry with materialThe organic layer was dried over sodium sulfate anhydrate
  8. customthe solvent was evaporated to dryness
  9. customThe residue was purified by silica gel column chromatography (CHCl3-Hexane)

Sources & evidence

ORD record
ord-b417832a5a124c44916a2fef3da95545
Source dataset
uspto-grants-2014_04
Patent number
US08697742B2

Linked notes

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