Diisopropylamine → (R)-3-[2-(3-hydroxypyrrolidin-1-yl)ethyl]-5-methyl-2H-isoquinolin-1-one

温度

-78 °C

Diisopropylamine (122 mL) was dissolved in tetrahydrofuran (400 mL), and n-butyllithium (1.56 mol/L) (534 mL) was added dropwise to the solution under ice-cooling. The mixture was stirred under ice-cooling for 30 min, and then cooled to −78° C. A solution (150 mL) of N,N-diethyl-2,3-dimethylbenzamide (85.4 g) in tetrahydrofuran was added dropwise to the reaction mixture and the mixture was stirred at −78° C. for 0.5 hr. The reaction mixture was cooled to −78° C. and absolution (150 mL) of (R)-1-(2-cyanoethyl)-3-hydroxypyrrolidine (53 g) in tetrahydrofuran was added dropwise to the mixture. The reaction mixture was allowed to warm to room temperature. After the completion of the reaction, water was added to the reaction mixture and the organic layer was separated and concentrated. The residue was dissolved in chloroform and the solution was washed with saturated brine and dried over magnesium sulfate. The organic layer was extracted with 1N hydrochloric acid, and the layer was basified. The aqueous layer was extracted with chloroform and the extract was dried over magnesium sulfate. The solvent was concentrated and the obtained residue was purified by silica gel column chromatography to give (R)-3-[2-(3-hydroxypyrrolidin-1-yl)ethyl]-5-methyl-2H-isoquinolin-1-one (23.6 g).

1. temperaturecooling
2. temperaturecooling for 30 min
3. stirringthe mixture was stirred at −78° C. for 0.5 hr
4. temperatureThe reaction mixture was cooled to −78° C.
5. temperatureto warm to room temperature
6. additionwas added to the reaction mixture
7. customthe organic layer was separated
8. concentrationconcentrated
9. dissolutionThe residue was dissolved in chloroform
10. washthe solution was washed with saturated brine
11. dry with materialdried over magnesium sulfate
12. extractionThe organic layer was extracted with 1N hydrochloric acid
13. extractionThe aqueous layer was extracted with chloroform
14. dry with materialthe extract was dried over magnesium sulfate
15. concentrationThe solvent was concentrated
16. customthe obtained residue was purified by silica gel column chromatography

ORDレコード

ord-2beaeea2c72a45799e514481d598fd73

出典データセット

uspto-grants-2007_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07220759B2