Hexane → 6-(2,6-Diethyl-phenyl)-4-methoxy-nicotinic acid methyl ester

HRID 251592Notes

Reaction equation

HRID 251592 reaction equation
[CH3:1][O:2][C:3](=[O:13])[C:4]1[C:9]([O:10][CH3:11])=[CH:8][C:7](Cl)=[N:6][CH:5]=1.[CH2:14]([C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([CH2:22][CH3:23])[C:17]=1B(O)O)[CH3:15].C([O-])([O-])=O.[Na+].[Na+].CCCCCC>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:13])[C:4]1[C:9]([O:10][CH3:11])=[CH:8][C:7]([C:17]2[C:18]([CH2:22][CH3:23])=[CH:19][CH:20]=[CH:21][C:16]=2[CH2:14][CH3:15])=[N:6][CH:5]=1

Participants

7

Reactant 4

HCID 8058HexaneHCID 10340Sodium CarbonateHCID 18437832(2,6-Diethylphenyl)boronic acidHCID 22498691Methyl 6-chloro-4-methoxypyridine-3-carboxylate

Product 1

HCID 596780886-(2,6-Diethyl-phenyl)-4-methoxy-nicotinic acid methyl ester

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 6-chloro-4-methoxy-nicotinic acid methyl ester (4.0 g, 19.8 mmol), 2,6-diethylphenyl boronic acid (7.0 g, 39.3 mmol), Na2CO3 (2M in H2O, 39 mL) and Pd(PPh3)4 (2.0 g, 1.7 mmol) in toluene (200 mL) is heated overnight at 80° C. under argon. On cooling, hexane (200 mL) is added and the organic layer separated. The organic layer is washed with 1N NaOH and water, dried (Na2SO4) and concentrated. The residue is purified by silica gel column (hexane/EtOAc 4:1) to give 6-(2,6-diethyl-phenyl)-4-methoxy-nicotinic acid methyl ester. 1H NMR (CDCl3) 8.99 (s, 1H), 7.30 (m, 1H), 7.15 (d, 2H), 6.89 (s, 1H), 3.95 (s, 3H), 3.94 (s, 3H), 2.34 (m, 4H), 1.06 (t, 6H).

Workup

  1. temperatureOn cooling
  2. customthe organic layer separated
  3. washThe organic layer is washed with 1N NaOH and water
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customThe residue is purified by silica gel column (hexane/EtOAc 4:1)

Sources & evidence

ORD record
ord-be19314fb0df42588c7cc9a443f1bdfb
Source dataset
uspto-grants-2011_01
Patent number
US07863454B2

Reaction notes

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