Isopropyl iodide → Methyl 2-(3-cyano-4-isopropoxyphenyl)isonicotinate

HRID 562913

Reaction equation

HRID 562913 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([C:10]2[CH:11]=[C:12]([CH:17]=[CH:18][N:19]=2)[C:13]([O:15][CH3:16])=[O:14])[CH:6]=[CH:7][C:8]=1[OH:9])#[N:2].[CH:20](I)([CH3:22])[CH3:21].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O>[C:1]([C:3]1[CH:4]=[C:5]([C:10]2[CH:11]=[C:12]([CH:17]=[CH:18][N:19]=2)[C:13]([O:15][CH3:16])=[O:14])[CH:6]=[CH:7][C:8]=1[O:9][CH:20]([CH3:22])[CH3:21])#[N:2]

Participants

7

Reactant 3

HCID 6362Isopropyl iodideHCID 11430Potassium CarbonateHCID 136368377Methyl 2-(3-cyano-4-hydroxyphenyl)isonicotinate

Product 1

HCID 66995041Methyl 2-(3-cyano-4-isopropoxyphenyl)isonicotinateYield 95.2%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

In 5 ml of DMF were dissolved 82 mg of methyl 2-(3-cyano-4-hydroxyphenyl)isonicotinate and 66 mg of isopropyl iodide, and the resulting solution was heated at 80° C. for 3 hours in the presence of 72 mg of potassium carbonate and 10 mg of tetra-n-butylammonium bromide. The reaction solution was cooled and then diluted with water, followed by extraction with ethyl acetate. The organic layer was washed with brine and then dried and concentrated under reduced pressure. The resulting residue was washed with a mixed solvent (hexane:ethyl acetate=10:1) to obtain 91 mg of methyl 2-(3-cyano-4-isopropoxyphenyl)isonicotinate. (2) Then, 86 mg of the compound was dissolved in a mixed solution of 3 ml of methanol and 3 ml of THF, and 0.35 ml of a 1M aqueous sodium hydroxide solution was added thereto, followed by heating at 60° C. for 1 hour. After being cooled to room temperature, the resulting solution was diluted with diisopropyl ether and water and an aqueous layer was separated. The aqueous layer was neutralized with 1M hydrochloric acid and then extracted with ethyl acetate. After being washed with water, the organic layer was dried and concentrated under reduced pressure to obtain 55 mg of 2-(3-cyano-4-isopropoxyphenyl)isonicotinic acid.

Workup

  1. temperatureThe reaction solution was cooled
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer was washed with brine
  4. customdried
  5. concentrationconcentrated under reduced pressure
  6. washThe resulting residue was washed with a mixed solvent (hexane:ethyl acetate=10:1)

Sources & evidence

ORD record
ord-f3e080e16a49494697220dc0092501c6
Source dataset
uspto-grants-2011_11
Patent number
US08067446B2

Linked notes

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