2-Bromoanisole → 2-Chloro-5-(2-methoxybenzoyl)pyridine

HRID 1516889Notes

Reaction equation

HRID 1516889 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[O:8][CH3:9].[Li]CCCC.[Cl:15][C:16]1[CH:27]=[CH:26][C:19]([C:20](N(OC)C)=[O:21])=[CH:18][N:17]=1>C1COCC1>[Cl:15][C:16]1[N:17]=[CH:18][C:19]([C:20]([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[O:8][CH3:9])=[O:21])=[CH:26][CH:27]=1

Participants

5

Reactant 3

HCID 113582-BromoanisoleHCID 114355976-Chloro-N-methoxy-N-methylnicotinamideHCID 178418339Butyllithium

Product 1

HCID 202271802-Chloro-5-(2-methoxybenzoyl)pyridineYield 50.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 1-bromo-2-methoxy-benzene (49.2 g, 0.263 mol) in dry THF (500 mL) was added dropwise n-BuLi (2.5 M in hexane, 105 mL, 0.263 mol) at −78° C. under N2 atmosphere. The mixture was stirred at this temperature for 1 hr and then a solution of 6-chloro-N-methoxy-N-methyl-nicotinamide (50 g, 0.25 mol) in THF (100 mL) was added dropwise. The reaction mixture was warmed to room temperature, stirred overnight and then was quenched with a saturated solution of NH4Cl (300 mL). The separated aqueous layer was extracted with ethyl acetate (3×300 mL). The combined organic layers were washed with brine, dried over Na2SO4, evaporated in vacuo to give the crude product that was purified by column chromatography to yield (6-chloropyridin-3-yl)-(2-methoxyphenyl)-methanone as a white solid (31 g, 47.6%).

Workup

  1. stirringstirred overnight
  2. customwas quenched with a saturated solution of NH4Cl (300 mL)
  3. extractionThe separated aqueous layer was extracted with ethyl acetate (3×300 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. customevaporated in vacuo
  7. customto give the crude product that
  8. customwas purified by column chromatography

Sources & evidence

ORD record
ord-23c5ad21d6ac421aa17cf49a4b17088c
Source dataset
uspto-grants-2012_07
Patent number
US08227615B2

Reaction notes

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