Sodium Bicarbonate → 2-Chloro-5-(3,5-dimethylphenyl)nicotinic acid

HRID 1675936Notes

Reaction equation

HRID 1675936 reaction equation
[Cl:1][C:2]1[N:11]=[CH:10][C:9](I)=[CH:8][C:3]=1[C:4]([O:6]C)=[O:5].[CH3:13][C:14]1[CH:15]=[C:16](B(O)O)[CH:17]=[C:18]([CH3:20])[CH:19]=1.C(=O)(O)[O-].[Na+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[N:11]=[CH:10][C:9]([C:16]2[CH:17]=[C:18]([CH3:20])[CH:19]=[C:14]([CH3:13])[CH:15]=2)=[CH:8][C:3]=1[C:4]([OH:6])=[O:5]

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 27343493,5-Dimethylphenylboronic acidHCID 2764559Methyl 2-Chloro-5-iodonicotinate

Product 1

HCID 532227192-Chloro-5-(3,5-dimethylphenyl)nicotinic acid

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a deoxygenated solution of methyl 2-chloro-5-iodonicotinate (1-1, 2.01 g, 6.72 mmol, 1 equiv) and 3,5-dimethylphenylboronic acid (1.01 g, 6.72 mmol. 1.00 equiv) in dioxane (250 mL) was added tetrakis(triphenylphosphine)palladium(0) (155 mg, 0.134 mmol) and 2 N aqueous sodium bicarbonate solution (16.8 mL, 33.6 mmol, 5.00 equiv) and the reaction mixture was heated at 90° C. for 48 hours. The reaction mixture was allowed to cool to 23° C., then partitioned between ethyl acetate (500 mL) and saturated aqueous sodium bicarbonate solution (500 mL). The aqueous layer was filtered and acidified to pH 2 with concentrated hydrochloric acid. The resulting precipitate was collected by filtration washed with water (2×100 mL) and air dried to afford 2-chloro-5-(3,5-dimethylphenyl)nicotinic acid (1-2) as an off white solid. LRMS m/z (M+H) 262.3 found, 262.1 required.

Workup

  1. temperatureto cool to 23° C.
  2. custompartitioned between ethyl acetate (500 mL) and saturated aqueous sodium bicarbonate solution (500 mL)
  3. filtrationThe aqueous layer was filtered
  4. filtrationThe resulting precipitate was collected by filtration
  5. washwashed with water (2×100 mL) and air
  6. customdried

Sources & evidence

ORD record
ord-1c74436cddf243959dbb29a72284dee6
Source dataset
uspto-grants-2011_08
Patent number
US08003797B2

Reaction notes

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