Dichloromethane → tert-Butyl methyl 5-(5-methylpyridin-2-yl)isophthalate

HRID 888375Notes

Reaction equation

HRID 888375 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:15]([O:17][CH3:18])=[O:16])[CH:5]=[C:6]([CH:14]=1)[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8].[Br-].[CH3:20][C:21]1[CH:22]=[CH:23][C:24]([Zn+])=[N:25][CH:26]=1.[K+].[K+].[K+].C(N(CC([O-])=O)CC(O)=O)CN(CC([O-])=O)CC([O-])=O.ClCCl>O1CCCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH3:20][C:21]1[CH:22]=[CH:23][C:24]([C:2]2[CH:3]=[C:4]([C:15]([O:17][CH3:18])=[O:16])[CH:5]=[C:6]([CH:14]=2)[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])=[N:25][CH:26]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 62717Edetate TripotassiumHCID 66896065Tert-butyl methyl 5-bromoisophthalateHCID 178427808HCID 178427808, compound

Product 1

HCID 68499855tert-Butyl methyl 5-(5-methylpyridin-2-yl)isophthalate

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of tert-butyl methyl 5-bromoisophthalate (10.6 g, 33.6 mmol) and bis(tri-tert-butylphosphine)palladium(0) (0.31 g, 0.61 mmol) in tetrahydrofuran (160 mL) was added 5-methyl-2-pyridylzinc bromide (0.5 M in THF; 121 mL, 60.5 mmol). The reaction mixture was heated to 60° C. After 18 h, the reaction was cooled to ambient temperature. Aqueous ethylenediaminetetraacetic acid tripotassium salt (0.4 M, 100 mL) and dichloromethane (100 mL) were added. The mixture was stirred for 15 min and the organic solvent was evaporated. The mixture was extracted with dichloromethane (3×). The combined organic extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (99% hexanes/ethyl acetate→50% hexanes/ethyl acetate) gave the title compound. MS 328.1 (M+1).

Workup

  1. temperaturethe reaction was cooled to ambient temperature
  2. customthe organic solvent was evaporated
  3. extractionThe mixture was extracted with dichloromethane (3×)
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by silica gel chromatography (99% hexanes/ethyl acetate→50% hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-11bf9e874481447b84115655bc675d74
Source dataset
uspto-grants-2012_08
Patent number
US08247401B2

Reaction notes

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