Hydrogen Peroxide → 5-Chloro-6-((3,3-difluorocyclobutyl)methoxy)pyridin-3-OL

HRID 512061Notes

Reaction equation

HRID 512061 reaction equation
[Cl:1][C:2]1[C:3]([O:17][CH2:18][CH:19]2[CH2:22][C:21]([F:24])([F:23])[CH2:20]2)=[N:4][CH:5]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:7]=1.OO.S([O-])([O-:29])=S>CO>[Cl:1][C:2]1[CH:7]=[C:6]([OH:29])[CH:5]=[N:4][C:3]=1[O:17][CH2:18][CH:19]1[CH2:22][C:21]([F:24])([F:23])[CH2:20]1

Participants

5

Reactant 3

HCID 784Hydrogen PeroxideHCID 9548651Thiosulfite(2-)HCID 580424833-Chloro-2-((3,3-difluorocyclobutyl)methoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)pyridine

Product 1

HCID 580423895-Chloro-6-((3,3-difluorocyclobutyl)methoxy)pyridin-3-OLYield 81%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

3-Chloro-2-[(3,3-difluorocyclobutyl)methoxy]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (Preparation 38, 4.5 g, 12.5 mmol) was suspended in methanol (30 mL). Hydrogen peroxide (1.6 mL, 21.3 mmol) was added and the mixture stirred at room temperature under nitrogen for 16 hours. An aqueous solution of thiosulfite (10%, 10 mL) was added and the mixture was extracted with EtOAc (2×200 mL). The combined organics were dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (Biotage®, gradient of 0-50% EtOAc in heptane) to afford the title compound (2.53 g, 81%).

Workup

  1. extractionthe mixture was extracted with EtOAc (2×200 mL)
  2. dry with materialThe combined organics were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by silica gel chromatography (Biotage®, gradient of 0-50% EtOAc in heptane)

Sources & evidence

ORD record
ord-760529be6cd646738e14bb8ab900c714
Source dataset
uspto-grants-2015_08
Patent number
US09102621B2

Reaction notes

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