Thionyl Chloride → 3-(1-Acetyl-4-piperidinyl)propionyl chloride

3-(1-Acetyl-4-piperidinyl)propionic acid (8.10 g, 40.7 mmol) was added portionwise to thionyl chloride (40 ml, 550 mmol) with ice-bath cooling. After 5 minutes of stirring, the excess thionyl chloride was distilled off and the residue was washed with hexane to provide 3-(1-acetyl-4-piperidinyl)propionyl chloride as light-yellow solid. Aluminum chloride (15.8 g, 119 mmol) powders were then added portionwise to a mixed solution of the above acid chloride and 4-formyl-2,3,4,5-tetrahydro-1,4-benzoxazepine (6.00 g, 33.8 mmol) in 1,2-dichloroethane (30 ml) with ice-bath cooling. This mixture was then stirred at room temperature for 18 hours, at the end of which time it was poured in ice-water and extracted with ethyl acetate. The extract was washed with saturated NaCl/H2O and dried over MgSO4, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent: ethyl acetate-methanol=9:1) to provide 3-(1-acetyl-4-piperidinyl)-1-(4-formyl-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1-propanone (6.77 g) as light-yellow oil.

1. temperaturecooling
2. distillationthe excess thionyl chloride was distilled off
3. washthe residue was washed with hexane

ORD record

ord-99e17bfc630246679428810336fe3905

Source dataset

uspto-grants-2003_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06534496B1