Methyl 2-chloropyridine-4-carboxylate → Methyl 2-(3-cyano-4-isobutoxyphenyl)isonicotinate

HRID 562912Notes

Reaction equation

HRID 562912 reaction equation
[C:1]([C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[CH:7][C:8]=1[O:9][CH2:10][CH:11]([CH3:13])[CH3:12])#[N:2].Cl[C:18]1[CH:19]=[C:20]([CH:25]=[CH:26][N:27]=1)[C:21]([O:23][CH3:24])=[O:22]>C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+].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>[C:1]([C:3]1[CH:4]=[C:5]([C:18]2[CH:19]=[C:20]([CH:25]=[CH:26][N:27]=2)[C:21]([O:23][CH3:24])=[O:22])[CH:6]=[CH:7][C:8]=1[O:9][CH2:10][CH:11]([CH3:13])[CH3:12])#[N:2]

Participants

6

Reactant 2

HCID 2736842Methyl 2-chloropyridine-4-carboxylateHCID 54576546(3-Cyano-4-isobutoxyphenyl)boronic acid

Product 1

HCID 66995295Methyl 2-(3-cyano-4-isobutoxyphenyl)isonicotinateYield 95.7%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolventHCID 10340Sodium CarbonateSolvent

Procedure

In a mixed solution of 50 ml of toluene and 30 ml of a 2M aqueous sodium carbonate solution were dissolved 1.46 g of (3-cyano-4-isobutoxyphenyl)boronic acid and 1.86 g of methyl 2-chloroisonicotinate, and the resulting solution was heated at 100° C. for 1 hour in the presence of 0.49 g of tetrakis(triphenylphosphine)palladium. The reaction solution was extracted with ethyl acetate and the organic layer was washed with brine and then dried and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate:chloroform=70:15:15) to obtain 1.98 g of methyl 2-(3-cyano-4-isobutoxyphenyl)isonicotinate. (2) Then, 1.98 g of the compound was dissolved in a mixed solution of 30 ml of methanol and 70 ml of THF, and 9 ml of a 1M aqueous sodium hydroxide solution was added thereto, followed by heating at 50° C. for 1 hour.

Workup

  1. extractionThe reaction solution was extracted with ethyl acetate
  2. washthe organic layer was washed with brine
  3. customdried
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate:chloroform=70:15:15)

Sources & evidence

ORD record
ord-9d3e3f5ce118446193f19d53f19d1115
Source dataset
uspto-grants-2011_11
Patent number
US08067446B2

Reaction notes

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