Dimethylformamide → 3-Methyl-4-oxo-5-(2-piperidin-1-yl-ethyl)-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-c]azepine-2-carbaldehyde

Temperatur

-10 °C

Dichloromethane (36 ml, 559 mmol) and N,N-dimethylformamide (1.637 ml, 20.9 mmol) were stirred for 5 minutes at −15° C. in an ice-salt bath under an argon atmosphere. The solution was added dropwise with phosphorus oxychloride (1.07 ml, 11.5 mmol) and stirred for 15 minutes while maintaining the temperature at −10° C. 3-methyl-5-(2-piperidin-1-yl-ethyl)-5,6,7,8-tetrahydro-1H-pyrrolo[3,2-c]azepin-4-on e 32c (1.26 g, 4.58 mmol) was dissolved in 10 ml of dichloromethane, the resulting solution was added dropwise to the above solution. Upon completion of the addition, the ice-salt bath was removed, and the reaction mixture was stirred for 3 hours at room temperature. After thin lay chromatography showed the disappearance of starting materials, the reaction mixture was quenched with iced water, adjusted to about pH 10 with sodium hydroxide solution (10 mol/L) and stirred for 30 minutes, extracted with dichloromethane (30 ml×3). The combined organic extracts were washed with saturated brine (30 ml), dried over anhydrous magnesium sulfate, filtered to remove the drying agent and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound 3-methyl-4-oxo-5-(2-piperidin-1-yl-ethyl)-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-c]azepine-2-carbaldehyde 32d (993 mg, yield 71.4%) as a light yellow solid.

1. additionthe resulting solution was added dropwise to the above solution
2. additionUpon completion of the addition
3. customthe ice-salt bath was removed
4. stirringthe reaction mixture was stirred for 3 hours at room temperature
5. customthe reaction mixture was quenched with iced water
6. stirringstirred for 30 minutes
7. extractionextracted with dichloromethane (30 ml×3)
8. washThe combined organic extracts were washed with saturated brine (30 ml)
9. dry with materialdried over anhydrous magnesium sulfate
10. filtrationfiltered
11. customto remove the drying agent
12. concentrationconcentrated under reduced pressure
13. customThe residue was purified by silica gel column chromatography

ORD-Eintrag

ord-8353183ad76147789ac7b5a4daf9ae5f

Quelldatensatz

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08329682B2