Reaktion #57784

Reaktionsgleichung

chlorotrimethylsilane

2-bromopyridine

n-butyllithium

2-amino-5-chlorobenzoic acid

HCl

→

desired product

Ausbeute 45.1%

(2-amino-5-chloro-phenyl)-pyridin-2-yl-methanone

Ausbeute 45.1%

Lösungsmittel

Et2O

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwas added in one portion to the solution
2. 2
   Sonstigeprepared
3. 3
   workup.STIRRINGThe reaction mixture was stirred for 2 hrs at 0° C.
4. 4
   workup.STIRRINGwith stirring
5. 5
   SonstigeThe resulting two-phase system was separated
6. 6
   Extraktionextracted with ethyl acetate (2×150 ml)
7. 7
   ExtraktionThe combined organic extractions
8. 8
   Trocknenwere dried over Na2SO4
9. 9
   SonstigeAfter removal of solvent
10. 10
    Sonstigethe residue was purified by the flash chromatography
11. 11
    SonstigeCrystallization of the product from Et2O/hexane mixture

Vorschrift

To a solution of 2-bromopyridine (5 ml, 52 mmol) in Et2O (60 ml) was added 40 ml of a n-butyllithium (1.6M in hexane, 64 mmol) drop wise at −40° C. over 30 min under a nitrogen atmosphere. The resulting yellow solution was stirred for a further 1 hr at −50° C. to −30° C. In a separate flask, a solution of 2-amino-5-chlorobenzoic acid (2.05 g, 12 mmol) in dry THF (90 ml), under nitrogen atmosphere and with ice-cooling, was added in one portion to the solution prepared as described above. The reaction mixture was stirred for 2 hrs at 0° C. and then chlorotrimethylsilane (30 ml) was added at 0° C. with stirring. The reaction mixture was allowed to warm to room temperature and 1 N HCl aq (100 ml) was added. The resulting two-phase system was separated. The aqueous phase was adjusted to pH12 with 6N NaOH solution and extracted with ethyl acetate (2×150 ml). The combined organic extractions were dried over Na2SO4. After removal of solvent, the residue was purified by the flash chromatography using ethyl acetate/hexane (1:4) as eluent. Crystallization of the product from Et2O/hexane mixture gave 1.26 g (45%) of desired product as yellow solid. 1H-NMR (DMSO-d6, 500 MHz): δ 6.90 (1H, d, J=9 Hz), 7.31 (1H, dd, J=9 and 2.5 Hz), 7.40 (2H, br), 7.53 (1H, d, J=2.5 Hz), 7.61 (1H, m), 7.79 (1H, d, J=8 Hz), 8.03 (1H, m), 8.69 (1H, m). MS: (ESI+): 233.2 (M+1).

Quelle