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

HRID 1908719Notes

Reaction equation

HRID 1908719 reaction equation
[CH2:1]([O:3][C:4](=[O:13])[C:5]1[CH:10]=[C:9]([CH3:11])[N:8]=[C:7](Cl)[CH:6]=1)[CH3:2].[C:14]1(P(C2C=CC=CC=2)C2C=CC=CC=2)[CH:19]=CC=C[CH:15]=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]([CH:11]=[C:14]([CH3:19])[CH3:15])[N:8]=[C:7]([CH3:33])[CH:6]=1)[CH3:2]

Participants

8

Reactant 4

HCID 947NitrogenHCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 22625009Ethyl 2-Chloro-6-methylisonicotinate

Product 1

HCID 574371992-Methyl-6-(2-methylpropenyl)isonicotinic acid ethyl ester

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

To a solution of 2-chloro-6-methylisonicotinic acid ethyl ester (9.92 g, 49.7 mmol), 2,4,6-tris-(2-methyl-propenyl)-cycloboroxane pyridine complex (13.0 g, 49.7 mmol, prepared in analogy to a procedure given by F. Kerins, D. F. O'Shea J. Org. Chem. 67 (2002) 4968-4971), and triphenylphosphine (1.39 g, 8.60 mmol) in DME (120 mL), a solution of 2 M aq. K2CO3 (40 mL) is added. The mixture is degassed and flushed with N2 before Pd(PPh3)4 (580 mg, 0.793 mmol) is added. The mixture is stirred at 100° C. for 20 h before it is cooled to rt, diluted with EA and washed with sat. aq. NaHCO3 (2×200 mL). The org. extract is dried over MgSO4, filtered and evaporated. The crude product is purified by CC on silica gel eluting with heptane:EA 15:1 to give 2-methyl-6-(2-methyl-propenyl)-isonicotinic acid ethyl ester (9.90 g) as a yellow oil; LC-MS: tR=0.44 min; 1H NMR (CDCl3): δ 1.43 (m, 3H), 1.98 (s, 3H), 2.09 (s, 3H), 2.63 (s, 3H), 4.34-4.46 (m, 2H), 6.39 (s, 1H), 7.50 (s, 1H), 7.56 (s, 1H).

Workup

  1. customThe mixture is degassed
  2. additionis added
  3. temperatureis cooled to rt
  4. washwashed with sat. aq. NaHCO3 (2×200 mL)
  5. extractionextract
  6. dry with materialis dried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customThe crude product is purified by CC on silica gel eluting with heptane:EA 15:1

Sources & evidence

ORD record
ord-1c06045106e04811a501c0ad3152aaea
Source dataset
uspto-grants-2013_12
Patent number
US08598208B2

Reaction notes

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