1(2H)-Isoquinolinone → 2-(4-fluorobenzyl)isoquinolin-1(2H)-one

Temperature

0 °C

According to Scheme 11: To a solution of NaHMDS (2 eq, 3.00 mmol, 0.50 g) in THF (3 mL) at 0° C. was added isoquinolin-1(2H)-one (1 eq, 1.00 mmol, 0.20 g) dissolved in THF (3 mL) and DMF (5 mL). The reaction mixture was stirred for 10 min at 0° C. then cooled at −70° C. The 1-(bromomethyl)-4-fluorobenzene (4 eq, 4.00 mmol, 0.80 g) was added in one portion to the reaction mixture. The reaction mixture was allowed to warm to room temperature, for one hour. Upon completion the reaction mixture was concentrated under vacuum and the crude residue partitioned between water and AcOEt, the aqueous layer was extracted with AcOEt. The combined organic layers were successively washed with water (2.30 mL), HCl (1M, 2.30 mL), brine (2.20 mL), dried over Na2SO4, filtered and evaporated to afford a yellow oil. The crude compound was purified on silica gel using cyclohexane/AcOEt 80/20 as eluent to afford 2-(4-fluorobenzyl)isoquinolin-1(2H)-one as a white solid (0.70 mmol, 0.26 g, 74%).

1. temperaturethen cooled at −70° C
2. temperatureto warm to room temperature, for one hour
3. concentrationUpon completion the reaction mixture was concentrated under vacuum
4. customthe crude residue partitioned between water and AcOEt
5. extractionthe aqueous layer was extracted with AcOEt
6. washThe combined organic layers were successively washed with water (2.30 mL), HCl (1M, 2.30 mL), brine (2.20 mL)
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. customevaporated
10. customto afford a yellow oil
11. customThe crude compound was purified on silica gel

ORD record

ord-c139dc6613d6422ea6322b40f4a1c733

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08399493B2