Hydrochloric Acid → 4-[2-(5-Cyano-3-methyl-2-pyridin-3-yl-indol-1-yl)-ethoxy]-benzoic acid

HRID 1630807Notes

Reaction equation

HRID 1630807 reaction equation
C[O:2][C:3](=[O:31])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][CH2:12][N:13]2[C:21]3[C:16](=[CH:17][C:18]([C:22]#[N:23])=[CH:19][CH:20]=3)[C:15]([CH3:24])=[C:14]2[C:25]2[CH:26]=[N:27][CH:28]=[CH:29][CH:30]=2)=[CH:6][CH:5]=1.[OH-].[Li+].Cl>CO>[C:22]([C:18]1[CH:17]=[C:16]2[C:21](=[CH:20][CH:19]=1)[N:13]([CH2:12][CH2:11][O:10][C:7]1[CH:8]=[CH:9][C:4]([C:3]([OH:31])=[O:2])=[CH:5][CH:6]=1)[C:14]([C:25]1[CH:26]=[N:27][CH:28]=[CH:29][CH:30]=1)=[C:15]2[CH3:24])#[N:23]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 582157364-[2-(5-Cyano-3-methyl-2-pyridin-3-yl-indol-1-yl)-ethoxy]-benzoic acid methyl ester

Product 1

HCID 582156954-[2-(5-Cyano-3-methyl-2-pyridin-3-yl-indol-1-yl)-ethoxy]-benzoic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A flask is charged with 4-[2-(5-cyano-3-methyl-2-pyridin-3-yl-indol-1-yl)-ethoxy]-benzoic acid methyl ester (Example 61, 0.150 g, 0.36 mmol) in MeOH (5 mL). Aqueous lithium hydroxide (1 M, 0.912 mL, 0.912 mmol) is added and the mixture is refluxed overnight. The reaction mixture is then acidified to pH 1 using 1 M aqueous HCl solution and the methanol is removed in vacuo. The resulting solution is extracted with ethyl acetate. The organic layer is dried over sodium sulfate, filtered and concentrated. The resulting residue is purified by silica gel flash chromatography (dichloromethane-methanol, 9:1) to afford 4-[2-(5-cyano-3-methyl-2-pyridin-3-yl-indol-1-yl)-ethoxy]-benzoic acid as a white solid. 1H NMR (400 MHz, MeOD) δ ppm 2.27 (s, 3H), 4.22 (t, J=5.1 Hz, 2H), 4.60 (t, J=5.2 Hz, 2H), 6.72 (d, J=8.8 Hz, 2H), 7.57 (dd, J=8.6, 1.5 Hz, 1H), 7.62-7.72 (m, 1H), 7.76 (d, J=8.6 Hz, 1H), 7.86 (d, J=8.6 Hz, 2H), 8.02 (d, J=7.8 Hz, 1H), 8.07 (s, 1H), 8.72 (br. s., 2H). HRMS (ESI) m/z 398.1487 [(M+H)+ Calcd for C24H20N3O3: 398.1505].

Workup

  1. temperaturethe mixture is refluxed overnight
  2. customthe methanol is removed in vacuo
  3. extractionThe resulting solution is extracted with ethyl acetate
  4. dry with materialThe organic layer is dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulting residue is purified by silica gel flash chromatography (dichloromethane-methanol, 9:1)

Sources & evidence

ORD record
ord-57a33e9f4ca94fd484a526530fcc2539
Source dataset
uspto-grants-2014_07
Patent number
US08791141B2

Reaction notes

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