Sodium Hydroxide → 6-Chloro-2-(4-fluoroindolin-2-yl)pyridin-3-ol

HRID 595555Notes

Reaction equation

HRID 595555 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[NH:9][C:10]3[C:15]([CH:16]=2)=[C:14]([F:17])[CH:13]=[CH:12][CH:11]=3)[C:5]([OH:18])=[CH:4][CH:3]=1.[OH-].[Na+]>CCO>[Cl:1][C:2]1[N:7]=[C:6]([CH:8]2[CH2:16][C:15]3[C:10](=[CH:11][CH:12]=[CH:13][C:14]=3[F:17])[NH:9]2)[C:5]([OH:18])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 867262926-chloro-2-(4-fluoro-1H-indol-2-yl)pyridin-3-ol

Product 1

HCID 867262936-Chloro-2-(4-fluoroindolin-2-yl)pyridin-3-olYield 80%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 6-chloro-2-(4-fluoro-1H-indol-2-yl)pyridin-3-ol (10 g, 38 mmol) and metal Sn (23 g, 190 mmol) in CH3CH2OH/concentrated HCl (60 mL/40 mL) was stirred under reflux for 3 h. The mixture was cooled to room temperature and adjusted to pH=7 by saturated NaOH and filtered though a Celite pad. The filtrate was extracted with EtOAc, washed by brine, dried over Na2SO4 and concentrated. The residue was purified by silica gel chromatography (PE:EtOAc=10:1) to get 6-chloro-2-(4-fluoroindolin-2-yl)pyridin-3-ol (8 g, yield: 80%). 1H-NMR (CDCl3, 400 MHz) δ 9.86 (s, 1H), 7.10˜7.20 (m, 3H), 6.33˜6.91 (m, 2H), 5.15˜5.21 (m, 1H), 4.61 (s, 1H), 3.65˜3.71 (m, 1H), 3.04˜3.11 (m, 1H). MS (M+H)+: 265.

Workup

  1. temperatureunder reflux for 3 h
  2. filtrationfiltered though a Celite pad
  3. extractionThe filtrate was extracted with EtOAc
  4. washwashed by brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel chromatography (PE:EtOAc=10:1)

Sources & evidence

ORD record
ord-da1c0866e72143b5bd026a8a81a9bf34
Source dataset
uspto-grants-2016_01
Patent number
US09242998B2

Reaction notes

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