3-(Methylthio)-1-propanol → Methyl 2-{3-cyano-4-[3-(methylthio)propoxy]phenyl)isonicotinate

HRID 1162418Notes

Reaction equation

HRID 1162418 reaction equation
[CH3:1][S:2][CH2:3][CH2:4][CH2:5][OH:6].[C:7]([C:9]1[CH:10]=[C:11]([C:16]2[CH:17]=[C:18]([CH:23]=[CH:24][N:25]=2)[C:19]([O:21][CH3:22])=[O:20])[CH:12]=[CH:13][C:14]=1O)#[N:8].C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>C1COCC1>[C:7]([C:9]1[CH:10]=[C:11]([C:16]2[CH:17]=[C:18]([CH:23]=[CH:24][N:25]=2)[C:19]([O:21][CH3:22])=[O:20])[CH:12]=[CH:13][C:14]=1[O:6][CH2:5][CH2:4][CH2:3][S:2][CH3:1])#[N:8]

Participants

6

Reactant 4

HCID 104483-(Methylthio)-1-propanolHCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 136368377Methyl 2-(3-cyano-4-hydroxyphenyl)isonicotinate

Product 1

HCID 66995101Methyl 2-{3-cyano-4-[3-(methylthio)propoxy]phenyl)isonicotinateYield 68.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In 5 ml of THF were dissolved 63 mg of 3-(methylthio)-1-propanol and 100 mg of methyl 2-(3-cyano-4-hydroxyphenyl)isonicotinate, and the resulting solution was heated at 0° C. for 10 minutes in the presence of 0.15 ml of tributylphosphine and 149 mg of 1,1′-(azodicarbonyl)dipiperidine. Then, the reaction solution was warmed to room temperature and stirred all day and night. After removal of the solvent, water was added and extraction with ethyl acetate was performed. The resulting organic layer is washed with brine and then dried and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform:methanol=95:5) to obtain 92 mg of methyl 2-{3-cyano-4-[3-(methylthio)propoxy]phenyl}isonicotinate. (2) Then, 92 mg of the compound was dissolved in a mixed solution of 3 ml of methanol and 3 ml of THF, and 0.32 ml of a 1M aqueous sodium hydroxide solution was added thereto, followed by heating at 60° C. for 1 hour. After being cooled, the reaction solution was diluted with diisopropyl ether and an aqueous layer was separated. The aqueous layer was neutralized with 1M hydrochloric acid and then extracted with ethyl acetate. After washing with brine, the organic layer was dried and concentrated under reduced pressure to obtain 81 mg of 2-{3-cyano-4-[3-(methylthio)propoxy]phenyl}isonicotinic acid.

Workup

  1. customAfter removal of the solvent, water
  2. additionwas added
  3. extractionextraction with ethyl acetate
  4. washThe resulting organic layer is washed with brine
  5. customdried
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by silica gel column chromatography (chloroform:methanol=95:5)

Sources & evidence

ORD record
ord-8dfb2164dc544dc8997b75eee5b226a1
Source dataset
uspto-grants-2010_10
Patent number
US07820700B2

Reaction notes

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