Sodium Carbonate → 4-Chloro-6-(2,6-diethylphenyl)-2-trifluoromethyl-nicotinic acid methyl ester

HRID 1392621Notes

Reaction equation

HRID 1392621 reaction equation
[CH3:1][O:2][C:3](=[O:16])[C:4]1[C:9]([Cl:10])=[CH:8][C:7](Cl)=[N:6][C:5]=1[C:12]([F:15])([F:14])[F:13].[CH2:17]([C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([CH2:25][CH3:26])[C:20]=1B(O)O)[CH3:18].C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.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>[CH3:1][O:2][C:3](=[O:16])[C:4]1[C:9]([Cl:10])=[CH:8][C:7]([C:20]2[C:21]([CH2:25][CH3:26])=[CH:22][CH:23]=[CH:24][C:19]=2[CH2:17][CH3:18])=[N:6][C:5]=1[C:12]([F:15])([F:14])[F:13]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 18437832(2,6-Diethylphenyl)boronic acidHCID 596782074,6-Dichloro-2-trifluoromethyl-nicotinic acid methyl ester

Product 1

HCID 596783574-Chloro-6-(2,6-diethylphenyl)-2-trifluoromethyl-nicotinic acid methyl ester

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Procedure

A mixture of 4,6-dichloro-2-trifluoromethyl-nicotinic acid methyl ester (1.0 g, 3.7 mmol), 2,6-diethyl-phenyl boronic acid (0.78 g, 4.4 mmol), sodium carbonate (2 M aqueous solution, 4.4 mL, 8.8 mmol), and Pd(PPh3)4 (206 mg, 0.18 mmol) is refluxed in toluene for 48 hours and then cooled to room temperature. The organic layer is separated and the aqueous layer is extracted with ethyl acetate (2×50 mL). The combined organic layers are dried and the solvent removed. The crude product is purified by flash column (hexanes/ethyl acetate 8:1) to give 4-chloro-6-(2,6-diethyl-phenyl)-2-trifluoromethyl-nicotinic acid methyl ester as a white solid. 1H NMR: (CDCl3) 7.58 (s, 1H), 7.25 (t, 1H), 7.20 (d, 2H), 4.02 (s, 2.28 (q, 4H), 1.04 (t, 6H).

Workup

  1. customThe organic layer is separated
  2. extractionthe aqueous layer is extracted with ethyl acetate (2×50 mL)
  3. customThe combined organic layers are dried
  4. customthe solvent removed
  5. customThe crude product is purified by flash column (hexanes/ethyl acetate 8:1)

Sources & evidence

ORD record
ord-922bd46e0ba545a8835347a55f43918d
Source dataset
uspto-grants-2008_03
Patent number
US07342115B2

Reaction notes

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