Potassium Carbonate → 6-cyclopentyloxy-7-methoxy-1-(3-methoxy-benzyl)-1H-isoquinoline-2-carboxylic acid ethyl ester

Temperature

85 °C

To a stirred solution of 6-hydroxy-7-methoxy-1-(3-methoxy-benzyl)-1H-isoquinoline-2-carboxylic acid ethyl ester (890 mg, 2.41 mmol) in anhydrous N,N-dimethylformamide (25 mL) was added potassium carbonate (2.0 g, 14.5 mmol) and cyclopentyl iodide (0.84 mL, 7.24 mmol) dropwise. The reaction mixture was heated with stirring at 85° C. for 18 h. The solvent was evaporated and the residue was diluted with ethyl acetate (50 mL) and water (50 mL). The aqueous phase was extracted with ethyl acetate (3×50 mL). The combined extracts were washed with saturated aqueous sodium chloride solution (50 mL), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 70–230 mesh, 20% ethyl acetate/hexane) afforded 6-cyclopentyloxy-7-methoxy-1-(3-methoxy-benzyl)-1H-isoquinoline-2-carboxylic acid ethyl ester (350 mg, 32% yield) as a colorless oil.

1. temperatureThe reaction mixture was heated
2. customThe solvent was evaporated
3. additionthe residue was diluted with ethyl acetate (50 mL) and water (50 mL)
4. extractionThe aqueous phase was extracted with ethyl acetate (3×50 mL)
5. washThe combined extracts were washed with saturated aqueous sodium chloride solution (50 mL)
6. dry with materialdried over anhydrous magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo

ORD record

ord-b531bbb526bb4ef0b37c8a88092d65db

Source dataset

uspto-grants-2006_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07067529B2