Reaction #2146765

Reaction equation

7-Chloro-6-(piperidin-4-yloxy)-2H-isoquinolin-1-one

sodium cyanoborohydride

triethylamine

acetic acid

glyoxylic acid ethyl ester

→

[4-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yloxy)-piperidin-1-yl]-acetic acid ethyl ester

Solvents

methanol

Conditions

Workup

1. 1
   Filtrationthe reaction mixture was filtered
2. 2
   Otherthe filtrate was evaporated i
3. 3
   workup.DISSOLUTIONThe residue was dissolved in dichloromethane
4. 4
   Washwashed with 1 N NaOH and sat. NaCl-solution
5. 5
   DryingThe organic layer was dried with MgSO4
6. 6
   Otherevaporated
7. 7
   OtherThe obtained crude product
8. 8
   Otherwas used without further purification

Procedure

1.5 g (5.38 mmol) of 7-Chloro-6-(piperidin-4-yloxy)-2H-isoquinolin-1-one (7, free base) were dissolved in 100 mL of methanol. At room temperature, 1.09 g (10.8 mmol) of triethylamine, 3.23 g (53.8 mmol) of acetic acid, 7.63 g (33.6 mmol) of glyoxylic acid ethyl ester and molecular sieves (4 A) were added, followed by 253.6 mg (4.04 mmol) of sodium cyanoborohydride. After stirring for 2 h at room temperature, the reaction mixture was filtered and the filtrate was evaporated i. vac. The residue was dissolved in dichloromethane and washed with 1 N NaOH and sat. NaCl-solution. The organic layer was dried with MgSO4 and evaporated. The obtained crude product was used without further purification.

Source