Methyl 5-chloro-6-methoxypyridine-3-carboxylate → HCID 67026916, compound

HRID 1908782Notes

Reaction equation

HRID 1908782 reaction equation
[CH3:1][O:2][C:3](=[O:13])[C:4]1[CH:9]=[C:8](Cl)[C:7]([O:11][CH3:12])=[N:6][CH:5]=1>O1CCOCC1.C([O-])([O-])=O.[K+].[K+].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>[CH3:1][O:2][C:3](=[O:13])[C:4]1[CH:9]=[C:8]([CH:3]=[C:4]([CH3:9])[CH3:5])[C:7]([O:11][CH3:12])=[N:6][CH:5]=1

Participants

5

Reactant 1

HCID 15421661Methyl 5-chloro-6-methoxypyridine-3-carboxylate

Product 1

HCID 67026916HCID 67026916, compoundYield 62.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 11430Potassium CarbonateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 5-chloro-6-methoxy-nicotinic acid methyl ester (880 mg, 4.37 mmol) and 2,4,6-tri-(2-methyl-propenyl)-cycloboroxane pyridine complex (1.42 g, 4.37 mmol, prepared in analogy to a procedure given by F. Kerins, D. F. O'Shea J. Org. Chem. 67 (2002) 4968-4971) in dioxane (10 mL) and 2 M aq. K2CO3 solution (5 mL), Pd(PPh3)4 (101 mg, 87 μmol) is added after the mixture has been degassed and put under N2. The mixture is stirred at 80° C. for 18 h before it is cooled to rt, diluted with EA and washed with water. The org. extract is dried over MgSO4, filtered and concentrated. The crude product is purified by CC on silica gel eluting with heptane:EA 4:1 to give 6-methoxy-5-(2-methyl-propenyl)-nicotinic acid methyl ester (300 mg) as a colourless oil; LC-MS: tR=1.01 min; [M+1]+=222.00; 1H NMR (CDCl3): δ 1.85 (d, J=1.3 Hz, 3H), 1.97 (d, J=1.0 Hz, 3H), 3.93 (s, 3H), 4.04 (s, 3H), 6.20 (s, 1H), 8.04 (d, J=2.0 Hz, 1H), 8.71 (d, J=2.3 Hz, 1H).

Workup

  1. customhas been degassed
  2. temperatureis cooled to rt
  3. additiondiluted with EA
  4. washwashed with water
  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 4:1

Sources & evidence

ORD record
ord-16ea6fc6d5e34d86b1f2cf2bdf84c008
Source dataset
uspto-grants-2013_12
Patent number
US08598208B2

Reaction notes

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