Triethylborane → 6-(2,6-Diethyl-phenyl)-4-ethyl-2-methyl-nicotinic acid ethyl ester

HRID 1392654Notes

Reaction equation

HRID 1392654 reaction equation
[CH2:1]([O:3][C:4](=[O:23])[C:5]1[C:10](Cl)=[CH:9][C:8]([C:12]2[C:17]([CH2:18][CH3:19])=[CH:16][CH:15]=[CH:14][C:13]=2[CH2:20][CH3:21])=[N:7][C:6]=1[CH3:22])[CH3:2].[CH2:24](B(CC)CC)[CH3:25].C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.O.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:23])[C:5]1[C:10]([CH2:24][CH3:25])=[CH:9][C:8]([C:12]2[C:17]([CH2:18][CH3:19])=[CH:16][CH:15]=[CH:14][C:13]=2[CH2:20][CH3:21])=[N:7][C:6]=1[CH3:22])[CH3:2]

Participants

7

Reactant 3

HCID 7357TriethylboraneHCID 10340Sodium CarbonateHCID 59678345Ethyl 4-chloro-6-(2,6-diethylphenyl)-2-methylnicotinate

Product 1

HCID 669936416-(2,6-Diethyl-phenyl)-4-ethyl-2-methyl-nicotinic acid ethyl esterYield 64.3%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of 4-chloro-6-(2,6-diethyl-phenyl)-2-methyl-nicotinic acid ethyl ester (251 mg, 0.76 mmol), triethylborane (4.6 mL of 1 M solution in hexane, 4.6 mmol), Pd(PPh3)4 (26 mg, 0.023 mmol), and Na2CO3 (1.27 g, 6 mL of 2M solution in H2O) in toluene (20 mL) is heated for 48 hours at 95° C. After cooling to room temperature the mixture is diluted with water (10 mL) and extracted with EtOAc. The combined extracts are washed with saturated brine, dried (Na2SO4), concentrated, and purified by flash chromatography (elution with hexane/EtOAc 10:1) to yield 159 mg 6-(2,6-diethyl-phenyl)-4-ethyl-2-methyl-nicotinic acid ethyl ester as a colorless oil: 1H NMR (CDCl3) 7.29 (dd, 1H), 7.13 (d, 2H), 7.00 (s, 1H), 4.47 (q, 2H), 2.68 (q, 2H), 2.59 (s, 3H), 2.36-2.27 (m, 4H), 1.45 (t, 3H), 1.24 (t, 3H), 1.05 (t, 6H).

Workup

  1. temperatureAfter cooling to room temperature the mixture
  2. extractionextracted with EtOAc
  3. washThe combined extracts are washed with saturated brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. custompurified by flash chromatography (elution with hexane/EtOAc 10:1)

Sources & evidence

ORD record
ord-a00c803ef1224dbb8fef3d5273d98e51
Source dataset
uspto-grants-2008_03
Patent number
US07342115B2

Reaction notes

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