Reaktion #73472

Reaktionsgleichung

7-chloro-6-fluoro-isoquinoline-2-oxide

7-Chloro-6-fluoro-isoquinoline 2-oxide

tert-butylamine

p-toluenesulfonic anhydride

tert-butylamine

p-toluenesulfonic anhydride

→

pure desired product ( 95 )

Ausbeute 4.3%

tert-Butyl-(7-chloro-6-fluoro-isoquinolin-1-yl)-amine

Ausbeute 4.3%

Lösungsmittel

benzotrifluoride

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturbefore being cooled to 0° C.
2. 2
   workup.STIRRINGThe reaction mixture was stirred for 24 h at room temperature
3. 3
   Einengenconcentrated
4. 4
   Sonstigepartitioned between 120 mL of water and 150 mL of dichloromethane
5. 5
   SonstigeThe phases were separated
6. 6
   Waschenthe organic phase was washed eight times with 3N aqueous sodium hydroxide
7. 7
   Extraktionto extract excess p-toluenesulfonic acid
8. 8
   Trocknendried over magnesium sulphate
9. 9
   Filtrationfiltered
10. 10
    Sonstigeevaporated to dryness
11. 11
    SonstigeThe crude product was purified twice by silica gel chromatography (dichloromethane:methanol)

Vorschrift

A solution of 5.0 g (25.3 mmol) of 7-chloro-6-fluoro-isoquinoline-2-oxide (9) in 120 mL of benzotrifluoride was treated with 15.9 mL (11.1 g, 152 mmol) of tert-butylamine and cooled to 0° C. Then, 17.3 g (53.1 mmol) of p-toluenesulfonic anhydride were added portionwise with temperature control (<10° C.). The reaction mixture was stirred at room temperature for 16 h, before being cooled to 0° C. and another 8.0 mL (76.1 mmol) of tert-butylamine and 8.26 g (25.3 mmol) of p-toluenesulfonic anhydride were added. The reaction mixture was stirred for 24 h at room temperature, then concentrated and partitioned between 120 mL of water and 150 mL of dichloromethane. The phases were separated and the organic phase was washed eight times with 3N aqueous sodium hydroxide, to extract excess p-toluenesulfonic acid, dried over magnesium sulphate, filtered and evaporated to dryness. The crude product was purified twice by silica gel chromatography (dichloromethane:methanol) to give 277 mg of pure desired product (95) and 714 mg of the product slightly contaminated with p-toluenesulfonic acid. Rt=2.35 min (Method 2). Detected mass: 253.1 (M+H+).

Quelle