Ethyl 6-chloro-4-methylpyridine-2-carboxylate → HCID 66933544, compound

HRID 1908805Notes

Reaction equation

HRID 1908805 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH:5]=[C:4]([CH3:13])[CH:3]=1>COCCOC.C([O-])([O-])=O.[K+].[K+].C(OCC)C.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>[CH2:11]([O:10][C:8]([C:6]1[CH:5]=[C:4]([CH3:13])[CH:3]=[C:2]([CH:3]=[C:4]([CH3:13])[CH3:5])[N:7]=1)=[O:9])[CH3:12]

Participants

6

Reactant 1

HCID 46835592Ethyl 6-chloro-4-methylpyridine-2-carboxylate

Product 1

HCID 66933544HCID 66933544, compoundYield 64%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 3283Diethyl EtherSolventHCID 80711,2-DimethoxyethaneSolventHCID 11430Potassium CarbonateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of ethyl 6-chloro-4-methyl-pyridine-2-carboxylate (500 mg, 2.51 mmol) and 2,4,6-tris-(2-methyl-propenyl)-cyclotriboroxane pyridine complex (814 mg, 2.51 mmol) in DME (32 mL), 2 M aq. K2CO3 (12 mL) solution is added. The mixture is degassed and put under argon before Pd(PPh3)4 (52 mg, 0.045 mmol) is added. The mixture is stirred at 80° C. for 6 h before it is cooled to rt, diluted with diethyl ether (50 mL) and washed with sat. aq. NaHCO3 (2×30 mL) solution. The org. extract is dried over MgSO4, filtered and concentrated. The crude product is purified by CC on silica gel eluting with heptane:EA 9:1 to give 4-methyl-6-(2-methyl-propenyl)-pyridine-2-carboxylic acid ethyl ester (176 mg) as a yellow oil; 1H NMR (CDCl3): δ 1.45 (t, J=7.0 Hz, 3H), 1.97 (s, 3H), 2.12 (s, 3H), 2.42 (s, 3H), 4.46 (q, J=7.0 Hz, 2H), 6.41 (s, 1H), 7.17 (s, 1H), 7.75 (s, 1H).

Workup

  1. customThe mixture is degassed
  2. additionis added
  3. temperatureis cooled to rt
  4. washwashed with sat. aq. NaHCO3 (2×30 mL) solution
  5. extractionextract
  6. dry with materialis dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product is purified by CC on silica gel eluting with heptane:EA 9:1

Sources & evidence

ORD record
ord-c626c09eba8546dfb8bcdf4f61e1a96b
Source dataset
uspto-grants-2013_12
Patent number
US08598208B2

Reaction notes

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