Methyl chloroacetate → Methyl 5-isoquinolyloxyacetate

To an ice-cooled solution of 29.0 g of 5-hydroxyisoquinoline in 300 ml of DMF, 11.0 g of sodium methylate was added portionwise. After stirring for 30 min, 17.9 ml of methyl chloroacetate was added dropwise, and the resultant mixture was stirred at room temperature overnight and concentrated under reduced pressure. To the residue, 300 ml of toluene and 300 ml of water were added, and the whole mixture was filtered. The aqueous layer was extracted with 50 ml of toluene, and the combined toluene solution was treated with 2 g of charcoal and evaporated to give methyl 5-isoquinolyloxyacetate. The ester was dissolved in 100 ml of methanol, reacted with 80 ml of 3 N sodium hydroxide aqueous solution for 30 min. The reaction mixture was concentrated under reduced pressure, diluted with 80 ml of water and 160 ml of acetone, and neutralized with 20 ml of concentrated hydrochloric acid. The precipitates formed were filtered, washed with 80 ml of 50% aqueous acetone, and dried to give 34.5 g (85% yield) of the title compound.

1. additionwas added portionwise
2. concentrationconcentrated under reduced pressure
3. additionTo the residue, 300 ml of toluene and 300 ml of water were added
4. filtrationthe whole mixture was filtered
5. extractionThe aqueous layer was extracted with 50 ml of toluene
6. additionthe combined toluene solution was treated with 2 g of charcoal
7. customevaporated

ORD-Eintrag

ord-418f27570cd3459f8332b1ac697c0358

Quelldatensatz

uspto-grants-2001_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06313094B1