Water → 3-Hydroxy-5-chloropyridine

HRID 2406782Notes

Reaction equation

HRID 2406782 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([O:8][CH2:9][C@H:10]2[CH2:14][CH2:13][CH2:12][N:11]2[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH:5]=[N:6][CH:7]=1.C(=O)(O)[O-:23].[Na+].ClC1C=CC=C(C(OO)=O)C=1.O>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[N:6][CH:7]=1.[C:18]([O:17][C:15]([N:11]1[CH2:12][CH2:13][CH2:14][C@@H:10]1[CH2:9][O:8][C:4]1[CH:5]=[N+:6]([O-:23])[CH:7]=[C:2]([Cl:1])[CH:3]=1)=[O:16])([CH3:21])([CH3:20])[CH3:19]

Participants

7

Reactant 4

HCID 962WaterHCID 70297m-Chloroperbenzoic acidHCID 516892Sodium BicarbonateHCID 21309710(R)-tert-butyl 2-((5-chloropyridin-3-yloxy)methyl)pyrrolidine-1-carboxylate

Product 2

HCID 5823053-Hydroxy-5-chloropyridineHCID 66962069(R)-3-((1-(tert-butoxycarbonyl)pyrrolidin-2-yl)methoxy)-5-chloropyridine 1-oxide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred mixture of crude (R)-tert-butyl 2-((5-chloropyridin-3-yloxy)methyl)pyrrolidine-1-carboxylate (5.15 g, Ca. 11.28 mmol, EXAMPLE 29 Step 1) and sodium bicarbonate (2.77 g, 32.9 mmol) in dichloromethane was added m-chloroperbenzoic acid (mCPBA) (4.26 g, 24.7 mmol) at 0° C. The mixture was stirred at 0° C. for 30 min, and the mixture was warmed to room temperature during 30 min period. After being stirred at room temperature for 6 h, water was added to the mixture. The mixture was extracted with dichloromethane twice and washed with aq. sodium thiosulfate and brine. The extracts were combined and dried over sodium sulfate and concentrated in vacuo to afford an oil. The residual oil was purified by silica gel column chromatography (ethyl acetate/hexane 7:3 to ethyl acetate) to afford 2.709 g (73% from 5-chloropyridin-3-ol) of the title compound as a colorless viscous oil.

Workup

  1. temperaturethe mixture was warmed to room temperature during 30 min period
  2. stirringAfter being stirred at room temperature for 6 h
  3. extractionThe mixture was extracted with dichloromethane twice
  4. washwashed with aq. sodium thiosulfate and brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customto afford an oil
  8. customThe residual oil was purified by silica gel column chromatography (ethyl acetate/hexane 7:3 to ethyl acetate)

Sources & evidence

ORD record
ord-1406d2047918425185f2bcbe8acb26ef
Source dataset
uspto-grants-2014_08
Patent number
US08809380B2

Reaction notes

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