Reaction #710502

Reaction equation

NaBH4

BF3

2-Chloro-3-[(E)-2-nitrovinyl]-6-(trifluoromethyl)pyridine

→

hydrochloride

Yield 58.3%

2-[2-chloro-6-(trifluoromethyl)pyridin-3-yl]ethanamine

Solvents

HCl

tetrahydrofuran

tetrahydrofuran

Conditions

Workup

1. 1
   OtherThe resulting reaction mixture
2. 2
   Otherwas allowed to room temperature
3. 3
   workup.ADDITIONwas added to above reaction mixture at room temperature
4. 4
   OtherThe resulting reaction mixture
5. 5
   Otherwas allowed to room temperature
6. 6
   workup.STIRRINGstirred for 16 h
7. 7
   OtherAfter completion of reaction
8. 8
   Otherthe reaction mixture was quenched in ice water (200 mL)
9. 9
   Extractionextracted with ethyl acetate (3×200 mL)
10. 10
    WashThe combined organic layers were washed with water (1×100 mL), brine (1×100 mL)
11. 11
    Dryingdried over anhydrous sodium sulfate
12. 12
    Otherthe solvent was removed under reduced pressure
13. 13
    Otherto get crude amine
14. 14
    workup.STIRRINGstirred at room temperature for 2.0 h
15. 15
    ConcentrationThe reaction mixture was concentrated under reduced pressure

Procedure

To a stirred solution of NaBH4 (16.0 g, 4.2 eq.) in tetrahydrofuran (125 mL) was added BF3 etherate (125 mL) at 0° C. The resulting reaction mixture was allowed to room temperature and stirred for 15 min 2-Chloro-3-[(E)-2-nitrovinyl]-6-(trifluoromethyl)pyridine (Int-19) (25.0 g, 1.0 eq) in tetrahydrofuran (125 mL) was added to above reaction mixture at room temperature. The reaction mixture was heated to 70° C. and stirred for 2 h. The resulting reaction mixture was allowed to room temperature and stirred for 16 h. The progress of the reaction was monitored by TLC. After completion of reaction, the reaction mixture was quenched in ice water (200 mL) and extracted with ethyl acetate (3×200 mL). The combined organic layers were washed with water (1×100 mL), brine (1×100 mL), dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure to get crude amine. The amine compound was dissolved in ethanolic HCl (50 mL) and stirred at room temperature for 2.0 h. The reaction mixture was concentrated under reduced pressure to get crude 2-[2-chloro-6-(trifluoromethyl)pyridin-3-yl]ethanamine (IIb-35) hydrochloride (15.0 g, 58.3%).

Source