Ethyl Acetate → 2-[2-(4-Bromo-2-chloro-phenoxy)-acetylamino]-isonicotinic acid methyl ester

HRID 1945433Notes

Reaction equation

HRID 1945433 reaction equation
[Br:1][C:2]1[CH:12]=[CH:11][C:5]([O:6][CH2:7][C:8]([OH:10])=O)=[C:4]([Cl:13])[CH:3]=1.[CH3:14][O:15][C:16](=[O:24])[C:17]1[CH:22]=[CH:21][N:20]=[C:19]([NH2:23])[CH:18]=1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(OCC)(=O)C>CN(C1C=CN=CC=1)C.CN(C=O)C>[CH3:14][O:15][C:16](=[O:24])[C:17]1[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C:8](=[O:10])[CH2:7][O:6][C:5]2[CH:11]=[CH:12][C:2]([Br:1])=[CH:3][C:4]=2[Cl:13])[CH:18]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 236984Methyl 2-aminopyridine-4-carboxylateHCID 6931572-(4-Bromo-2-chlorophenoxy)acetic acidHCID 2724699PyBOP

Product 1

HCID 248120962-[2-(4-Bromo-2-chloro-phenoxy)-acetylamino]-isonicotinic acid methyl esterYield 56%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

To solution of (4-bromo-2-chloro-phenoxyacetic acid (100 mg, 0.378 mmol), 2-amino isonicotinic acid methyl ester (86.42 mg, 0.568 mmol) and DMAP (69.43 mg, 0.568 mmol) in DMF 2 mL was added PyBOP (295 mg, 0.568 mmol) at room temperature. Reaction mixture was stirred at room temperature. Resulting mixture poured onto ice cold water, was diluted by ethyl acetate. The organic phase was separated, sequentially washed with aqueous sodium bicarbonate, brine and water, dried over anhydrous MgSO4, and concentrated. The residue was purified by flash silica gel column chromatography (EtoAC:Hexane=1:9˜4:6) to give 2-[2-(4-bromo-2-chloro-phenoxy)-acetylamino]-isonicotinic acid methyl ester as a colorless solid (0.084 g, 56% yield).

Workup

  1. customReaction mixture
  2. customResulting mixture
  3. additionpoured onto ice cold water
  4. customThe organic phase was separated
  5. washsequentially washed with aqueous sodium bicarbonate, brine and water
  6. dry with materialdried over anhydrous MgSO4
  7. concentrationconcentrated
  8. customThe residue was purified by flash silica gel column chromatography (EtoAC:Hexane=1:9˜4:6)

Sources & evidence

ORD record
ord-f6c65c6971ce41d794aeffbb4f7fb94f
Source dataset
uspto-grants-2013_03
Patent number
US08394799B2

Reaction notes

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