3-Hydroxypyridine → HCID 10255652, compound

HRID 750850Notes

Reaction equation

HRID 750850 reaction equation
[CH3:1][S:2]([C:5]1[N:10]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=2[Cl:18])[C:8]([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=2)=[C:7](S(C)(=O)=O)[N:6]=1)(=[O:4])=[O:3].[OH:30][C:31]1[CH:32]=[N:33][CH:34]=[CH:35][CH:36]=1.C([Li])CCC>C1COCC1>[CH3:1][S:2]([C:5]1[N:6]=[C:7]([O:30][C:31]2[CH:32]=[N:33][CH:34]=[CH:35][CH:36]=2)[C:8]([C:19]2[CH:20]=[CH:21][C:22]([Cl:25])=[CH:23][CH:24]=2)=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=2[Cl:18])[N:10]=1)(=[O:4])=[O:3]

Participants

5

Reactant 3

HCID 79713-HydroxypyridineHCID 597538832,4-Bis(methylsulfonyl)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidineHCID 178418339Butyllithium

Product 1

HCID 10255652HCID 10255652, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a 50 mL round bottom flask fitted with a magnetic stirrer bar and rubber septum was added 20 mL anhydrous THF (Aldrich) and 2,4-bis(methyl-sulfonyl)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine (Reference Example 5) (1.0 g, 2 mmol). The flask was flushed with nitrogen and cooled to 0° C. In a separate flask, also fitted with a magnetic stirrer bar and rubber septum, was added 10 mL anhydrous THF and 3-hydroxypyridine (213 mg, 2.24 mmol), This flask was flushed with nitrogen and cooled to 0° C. Then n-butyl lithium (1.12 mL, 2.24 mmol) (Aldrich-2M solution in hexane) was added via syringe and the solution stirred for several minutes. The lithium alkoxide solution was then withdrawn by syringe and slowly added to the first reaction flask. The solution was stirred at 0° C. for 1 h, quenched with saturated sodium bicarbonate and the reaction products extracted with ethyl acetate. The organic layer was dried over anhydrous MgSO4, filtered and the solvent removed under reduced pressure. Flash column chromatography on silica gel (eluted with 35/65 hexanes/ethyl acetate) afforded 2-methylsulfonyl-4-(3-pyridyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine: 1H-NMR 500 MHz (CDCl3): δ 3.20 (s, 3H), 7.20-7.25 (m, 4H), 7.30-7.38 (m, 3H), 7.41 (m, 1H), 7.63-7.65 (m, 1H), 8.53-8.55 (m, 2H).

Workup

  1. customTo a 50 mL round bottom flask fitted with a magnetic stirrer bar
  2. customThe flask was flushed with nitrogen
  3. customIn a separate flask, also fitted with a magnetic stirrer bar
  4. customwas flushed with nitrogen
  5. temperaturecooled to 0° C
  6. customThe lithium alkoxide solution was then withdrawn by syringe
  7. additionslowly added to the first reaction flask
  8. stirringThe solution was stirred at 0° C. for 1 h
  9. customquenched with saturated sodium bicarbonate
  10. extractionthe reaction products extracted with ethyl acetate
  11. dry with materialThe organic layer was dried over anhydrous MgSO4
  12. filtrationfiltered
  13. customthe solvent removed under reduced pressure

Sources & evidence

ORD record
ord-be19fcb7993f4346802a4d8bb8ea9d7d
Source dataset
uspto-grants-2008_07
Patent number
US07405221B2

Reaction notes

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