Thionyl Chloride → HCID 19419096, compound

HRID 864470Notes

Reaction equation

HRID 864470 reaction equation
S(Cl)([Cl:3])=O.[N:5]1[CH:10]=[CH:9][CH:8]=[C:7]([CH2:11][CH2:12][C:13]2[CH:21]=[CH:20][C:16]([C:17](O)=[O:18])=[CH:15][CH:14]=2)[CH:6]=1>CN(C=O)C>[ClH:3].[N:5]1[CH:10]=[CH:9][CH:8]=[C:7]([CH2:11][CH2:12][C:13]2[CH:21]=[CH:20][C:16]([C:17]([Cl:3])=[O:18])=[CH:15][CH:14]=2)[CH:6]=1

Participants

4

Reactant 2

HCID 24386Thionyl ChlorideHCID 3086864-(2-pyridin-3-ylethyl)benzoic acid

Product 1

HCID 19419096HCID 19419096, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Methyl 4-(2-(3-pyridyl)ethyl)benzoate was dissolved in methanol (10 ml) and a solution of potassium hydroxide (2.1 g, 37.3 mmol) in water (2 ml) added. The mixture was stirred overnight and the pH lowered to ca. 7 by the cautious addition of concentrated hydrochloric acid. Methanol (20 ml) was added and the suspension filtered, the filtrate concentrated to give an oil to which 2M HCl was added to bring the pH to 8. A solid precipitate formed, the solvent was removed under reduced pressure and the residue azeotroped with toluene (1×100 ml, 1×50 ml) to give crude 4-(2-(3-pyridyl)ethyl)benzoic acid. Thionyl chloride (10 ml) and dry DMF (100 μl) were added to the crude 4-(2-(3-pyridyl)ethyl)benzoic acid and the mixture heated under gentle reflux for 1.5 h. The excess thionyl chloride was removed under reduced pressure and the residue azeotroped with toluene (×2) to give crude 4-(2-(3-pyridyl)ethyl)benzoyl chloride hydrochloride as a solid. DCM (20 ml) was added and the resultant suspension treated with L-leucine ethyl ester hydrochloride (733 mg, 3.73 mmol), triethylamine (5.2 ml, 37.3 mmol) and DMAP (30 mg). The mixture was stirred for 1 h at room temperature, diluted with DCM (50 ml) and the solution washed with water (2×20 ml) and saturated brine (20 ml). The combined organics were dried over anhydrous magnesium sulphate, filtered and evaporated to give a yellow oil. Column chromatography (silica: 4% methanol in DCM) gave N-4-(2-(3-pyridyl)ethyl)benzoyl-L-leucine ethyl ester (378 mg, 28%) as a yellow solid.

Workup

  1. temperaturethe mixture heated
  2. temperatureunder gentle reflux for 1.5 h
  3. customThe excess thionyl chloride was removed under reduced pressure
  4. customthe residue azeotroped with toluene (×2)

Sources & evidence

ORD record
ord-25be41153dbf4ecca53d2b640b22dd20
Source dataset
uspto-grants-1996_10
Patent number
US05563151

Reaction notes

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