Réaction #217865

Équation de réaction

(2-phenylsulfonyl-pyridin-3-yl)-(2-chlorophenyl)methanone

acetic acid

N2

LiOH

H3PO4

4-acetylpyridine

→

title compound

(2-chlorophenyl)-[2-(2-hydroxy-2-pyridin-4-yl-vinyl)pyridin-3-yl]methanone phosphate

Solvants

CH2Cl2

DMSO

CH2Cl2

Conditions de réaction

Traitement

1. 1
   Autredark brown during the reaction
2. 2
   AutreCompletion of the reaction
3. 3
   AutreAfter completion of the reaction
4. 4
   Températurecool the reaction mixture to 15° C. with a cold-water bath
5. 5
   AutreQuench the reaction mixture in 10 min with 10% NaCl (150 ml)
6. 6
   workup.ADDITIONAt the end of the addition
7. 7
   Autrereaches approximately 27° C
8. 8
   LavageCombine the organic layers and wash with 10% NaCl (3×300 mL)
9. 9
   ConcentrationConcentrate the combined organic layers to dryness under vacuum
10. 10
    workup.DISSOLUTIONre-dissolve the residue in MeOH (4.3 volumes)
11. 11
    TempératureCool the reaction mixture to 20° C.
12. 12
    workup.STIRRINGStir the suspension for 4 h at 20° C.
13. 13
    Filtrationfilter
14. 14
    Lavagewash the precipitate with MeOH (2×15 mL)
15. 15
    Autredry under vacuum at 50° C.

Mode opératoire

The title compound may also be prepared by an alternative process, which is described below. Add (2-phenylsulfonyl-pyridin-3-yl)-(2-chlorophenyl)methanone (15 g) and 4-acetylpyridine (7.59 g; 1.5 eq) to DMSO (150 mL) under an inert atmosphere of N2. Heat the solution to 70° C., then add LiOH (4 g, 4 eq) in one portion. Stir the reaction mixture for 4 hours at that temperature. The mixture turns from red to dark brown during the reaction. Completion of the reaction may be checked by HPLC. After completion of the reaction, cool the reaction mixture to 15° C. with a cold-water bath, and add CH2Cl2 (150 mL). Quench the reaction mixture in 10 min with 10% NaCl (150 ml) containing acetic acid (9.58 mL; 4 eq). At the end of the addition, the temperature reaches approximately 27° C. Re-extract the aqueous layer with CH2Cl2 (150 ml). Combine the organic layers and wash with 10% NaCl (3×300 mL). Concentrate the combined organic layers to dryness under vacuum and re-dissolve the residue in MeOH (4.3 volumes). Cool the reaction mixture to 20° C., and add H3PO4 (85% w/w in water; 2.88 mL; 1 eq). Stir the suspension for 4 h at 20° C., filter, wash the precipitate with MeOH (2×15 mL) and dry under vacuum at 50° C. to yield the title compound as an orange solid.

Source