Nitrogen → 5-Methyl-6-(2-methylpropenyl)nicotinic acid ethyl ester

HRID 1908775Notes

Reaction equation

HRID 1908775 reaction equation
[CH2:1]([O:3][C:4](=[O:13])[C:5]1[CH:10]=[C:9]([CH3:11])[C:8](Cl)=[N:7][CH:6]=1)[CH3:2].C1(P([C:27]2[CH:32]=[CH:31]C=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:33]([O-])([O-])=O.[K+].[K+].N#N>COCCOC.CC(=O)OCC.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:13])[C:5]1[CH:10]=[C:9]([CH3:11])[C:8]([CH:33]=[C:32]([CH3:31])[CH3:27])=[N:7][CH:6]=1)[CH3:2]

Participants

8

Reactant 4

HCID 947NitrogenHCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 574371976-Chloro-5-methylnicotinic acid ethyl ester

Product 1

HCID 574371985-Methyl-6-(2-methylpropenyl)nicotinic acid ethyl ester

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 6-chloro-5-methyl-nicotinic acid ethyl ester (4.98 g, 24.9 mmol), 2,4,6-tri-(2-methyl-propenyl)-cycloboroxane pyridine complex (5.74 g, 17.7 mmol, prepared in analogy to a procedure given by F. Kerins, D. F. O'Shea J. Org. Chem. 67 (2002) 4968-4971), and triphenylphosphine (1.15 g, 4.4 mmol) in DME (60 mL), a solution of 2 M aq. K2CO3 (20 mL) is added. The mixture is degassed and flushed with N2 before Pd(PPh3)4 (460 mg, 0.4 mmol) is added. The mixture is stirred at 90° C. for 20 h before it is cooled to rt, diluted with EA (150 mL) and washed with sat. aq. NaHCO3 (2×50 mL). The org. extract is dried over MgSO4, filtered and evaporated. The crude product is purified by FC (SiO2, heptane-EA) to give 5-methyl-6-(2-methyl-propenyl)-nicotinic acid ethyl ester (3.98 g) as an orange oil; LC-MS: tR=0.72 min, [M+1]+=220.15.

Workup

  1. customThe mixture is degassed
  2. additionis added
  3. temperatureis cooled to rt
  4. washwashed with sat. aq. NaHCO3 (2×50 mL)
  5. extractionextract
  6. dry with materialis dried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customThe crude product is purified by FC (SiO2, heptane-EA)

Sources & evidence

ORD record
ord-f64463a9d7d743ca875212aa11eace94
Source dataset
uspto-grants-2013_12
Patent number
US08598208B2

Reaction notes

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