Potassium Carbonate → 2-Propenyl-6-methylisonicotinic acid ethyl ester

HRID 2040768Notes

Reaction equation

HRID 2040768 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].[CH:14](/B(O)O)=[CH:15]\[CH3:16].C([O-])([O-])=O.[K+].[K+]>COCCOC.CCOCC.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.C1C=CC(P(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])[N:8]=[C:7]([CH:14]=[CH:15][CH3:16])[CH:6]=1)[CH3:2]

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 6157276((1E)-prop-1-en-1-yl)boronic acidHCID 22625009Ethyl 2-Chloro-6-methylisonicotinate

Product 1

HCID 670271022-Propenyl-6-methylisonicotinic acid ethyl esterYield 109.6%

Reagents, catalysts & solvents 4

HCID 11776TriphenylphosphineCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 3283Diethyl EtherSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 2-chloro-6-methylisonicotinic acid ethyl ester (2.0 g, 10.0 mmol), and trans-propenyl boronic acid (1.30 g, 15.13 mmol) in DME (20 mL), a solution of 2 M aq. K2CO3 (3 mL) followed by Pd(PPh3)4 (150 mg, 0.205 mmol) and PPh3 (265 mg, 0.99 mmol) is added. The mixture is stirred at 100° C. for 15 h before it is cooled to rt, diluted with ether and washed with sat. aq. Na2CO3 (2×30 mL). The org. extract is dried over Na2SO4, filtered and evaporated. The crude product is purified by CC on silica gel eluting with heptane:EA 4:1 to give 2-propenyl-6-methylisonicotinic acid ethyl ester (2.25 g) as a colourless oil; LC-MS: tR=0.65 min, [M+1]+=206.33.

Workup

  1. additionis added
  2. temperatureis cooled to rt
  3. washwashed with sat. aq. Na2CO3 (2×30 mL)
  4. extractionextract
  5. dry with materialis dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude product is purified by CC on silica gel eluting with heptane:EA 4:1

Sources & evidence

ORD record
ord-c9e11eec016d4ce9ad764f8191977d31
Source dataset
uspto-grants-2013_11
Patent number
US08580824B2

Reaction notes

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