Reaction #710494

Reaction equation

1-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]butan-2-one

ammonium acetate

sodium cyanoborohydride

→

desired product

Yield 33.2%

3-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]butan-2-amine

Yield 33.2%

Solvents

methanol

Conditions

Workup

1. 1
   FiltrationAfter filtration
2. 2
   ConcentrationThe reaction mixture was concentrated to dryness and 30 mL of ethyl acetate
3. 3
   workup.ADDITIONwere added
4. 4
   WashThe organic phase was washed with an aqueous solution of 1 N sodium hydroxide, brine and water
5. 5
   Dryingdried over magnesium sulfate
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated to dryness
8. 8
   workup.DISSOLUTIONThe crude material was dissolved in 15 mL of 1 N hydrochloric acid
9. 9
   Extractionextracted with 15 mL of ethyl acetate
10. 10
    workup.ADDITIONAn aqueous solution of 1 N sodium hydroxide was added to the aqueous phase, which
11. 11
    Extractionwas subsequently extracted twice with 15 mL of ethyl acetate
12. 12
    DryingThe organic phase was dried over magnesium sulfate
13. 13
    Filtrationfiltered
14. 14
    Concentrationconcentrated to dryness

Procedure

0.64 g of 1-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]butan-2-one (Int-12) (0.0025 mol) were diluted in 5 mL of methanol. 7.0 g of molecular sieves 3 Å, 1.90 g (0.025 mol) of ammonium acetate and 0.39 g (0.0052 mol) of sodium cyanoborohydride were added. The reaction medium was stirred overnight at room temperature. After filtration, the pH was adjusted to 9 with an aqueous solution of 1 N sodium hydroxide. The reaction mixture was concentrated to dryness and 30 mL of ethyl acetate were added. The organic phase was washed with an aqueous solution of 1 N sodium hydroxide, brine and water; dried over magnesium sulfate, filtered and concentrated to dryness. The crude material was dissolved in 15 mL of 1 N hydrochloric acid and extracted with 15 mL of ethyl acetate. An aqueous solution of 1 N sodium hydroxide was added to the aqueous phase, which was subsequently extracted twice with 15 mL of ethyl acetate. The organic phase was dried over magnesium sulfate, filtered and concentrated to dryness. 0.21 g (32%) of desired product 1-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]butan-2-amine (IIa-16) were obtained, [M+1]=253.

Source