Dimethylformamide → 6-butoxy-4-formyl-7-methoxy-1-(3-methoxy-benzyl)-1H-isoquinoline-2-carboxylic acid ethyl ester

To anhydrous N,N-dimethylformamide (0.102 mL, 1.32 mmol) at 0° C. was added phosphorus oxychloride (0.053 mL, 0.58 mmol) dropwise. The mixture was warmed to room temperature and stirred for 30 minutes. The mixture was cooled in an ice-bath, 6-butoxy-7-methoxy-1-(3-methoxy-benzyl)-1H-isoquinoline-2-carboxylic acid ethyl ester (230 mg, 0.53 mmol) in dichloromethane (3 mL) was added dropwise. After addition was complete, the mixture was heated on an oil bath for 4 hrs at 80° C. The mixture was cooled to 0° C. and a solution of potassium acetate (154 mg, 1.56 mmol) in water (2 mL) was added slowly. The mixture was then heated at 80° C. for 20 minutes. The mixture was cooled, poured into water and diluted with dichloromethane (60 mL). The organic layer was washed water (2×20 mL), saturated aqueous sodium bicarbonate solution (20 mL), saturated aqueous sodium chloride solution (20 mL), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to afford 6-butoxy-4-formyl-7-methoxy-1-(3-methoxy-benzyl)-1H-isoquinoline-2-carboxylic acid ethyl ester (243 mg, 99% yield) as a yellow oil. The crude product was used without further purification.

1. temperatureThe mixture was cooled in an ice-bath
2. additionAfter addition
3. temperaturethe mixture was heated on an oil bath for 4 hrs at 80° C
4. temperatureThe mixture was cooled to 0° C.
5. temperatureThe mixture was then heated at 80° C. for 20 minutes
6. temperatureThe mixture was cooled
7. washThe organic layer was washed water (2×20 mL), saturated aqueous sodium bicarbonate solution (20 mL), saturated aqueous sodium chloride solution (20 mL)
8. dry with materialdried over anhydrous magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo

ORD record

ord-cfd5489e498a43cd99b9b9536b84669e

Source dataset

uspto-grants-2006_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07067529B2