Sodium Carbonate → Ethyl 4-chloro-6-(2,6-diethylphenyl)-2-methylnicotinate

HRID 1392618Notes

Reaction equation

HRID 1392618 reaction equation
[CH2:1]([O:3][C:4](=[O:14])[C:5]1[C:10]([Cl:11])=[CH:9][C:8](Cl)=[N:7][C:6]=1[CH3:13])[CH3:2].[CH2:15]([C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([CH2:23][CH3:24])[C:18]=1B(O)O)[CH3:16].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>[CH2:1]([O:3][C:4](=[O:14])[C:5]1[C:10]([Cl:11])=[CH:9][C:8]([C:18]2[C:19]([CH2:23][CH3:24])=[CH:20][CH:21]=[CH:22][C:17]=2[CH2:15][CH3:16])=[N:7][C:6]=1[CH3:13])[CH3:2]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2786748Ethyl 4,6-dichloro-2-methylnicotinateHCID 18437832(2,6-Diethylphenyl)boronic acid

Product 1

HCID 59678345Ethyl 4-chloro-6-(2,6-diethylphenyl)-2-methylnicotinate

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Procedure

A mixture of 4,6-dichloro-2-methyl-nicotinic acid ethyl ester (1.2 g, 5.1 mmol), 2,6-diethyl-phenyl boronic acid (2.18 g, 12.2 mmol), sodium carbonate (2 M aqueous solution, 12.2 mL, 24.4 mmol), and Pd(PPh3)4 (284 mg, 0.26 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 organic layers are combined, dried, and 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-methyl-nicotinic acid ethyl ester. 1H NMR: (CDCl3) 7.26 (t, 1H), 7.18 (s, 1H), 7.13 (d, 2H), 4.47 (q, 2H), 2.62 (s, 3H), 2.28 (q, 4H), 1.44 (t, 3H), 1.04 (t, 6H).

Workup

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

Sources & evidence

ORD record
ord-481bfc8fd0424b5b951ec98558ee2f66
Source dataset
uspto-grants-2008_03
Patent number
US07342115B2

Reaction notes

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