2-Bromopyridine → (2-Amino-5-chlorophenyl)(pyridin-2-yl)methanone

HRID 2053422Notes

Reaction equation

HRID 2053422 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.C([Li])CCC.[NH2:13][C:14]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:15]=1[C:16](O)=[O:17]>O1CCCC1>[NH2:13][C:14]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:15]=1[C:16]([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1)=[O:17]

Participants

5

Reactant 3

HCID 79732-BromopyridineHCID 124762-Amino-5-chlorobenzoic acidHCID 178418339Butyllithium

Product 1

HCID 288049(2-Amino-5-chlorophenyl)(pyridin-2-yl)methanoneYield 76.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a cooled solution (−40° C.) of 2-bromopyridine (1.68 mL, 17.6 mmol) in tetrahydrofuran (THF) (30 mL) was added n-butyllithium (nBuLi) (9.7 mL, 19 mmol, 2M in pentane) in a dropwise fashion and the resulting mixture was stirred for 30 min. 2-amino-5-chlorobenzoic acid (0.7 g, 4 mmol) was added and stirring was continued at 0° C. After 2 h, the mixture was quenched with trimethylchlorosilane (TMSCl) (10 mL), and hydrolyzed with 1N HCl (30 mL). The aqueous layer was separated from the organic phase, neutralized with 3N aq. sodium hydroxide, and extracted with ether (3×100 mL). The combined ether extracts were dried (Na2SO4), filtered, concentrated and purified by flash chromatography on silica gel [hexanes:ethyl acetate (7:3)] to give (2-amino-5-chlorophenyl)-pyridin-2-yl-methanone (0.71 g, 76%).

Workup

  1. stirringstirring
  2. customwas continued at 0° C
  3. waitAfter 2 h
  4. customthe mixture was quenched with trimethylchlorosilane (TMSCl) (10 mL)
  5. customThe aqueous layer was separated from the organic phase
  6. extractionextracted with ether (3×100 mL)
  7. dry with materialThe combined ether extracts were dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. custompurified by flash chromatography on silica gel [hexanes:ethyl acetate (7:3)]

Sources & evidence

ORD record
ord-5f26e0a376574e21a0c7bcf6d3c356f5
Source dataset
uspto-grants-2008_02
Patent number
US07326788B2

Reaction notes

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