Potassium Carbonate → Tert-butyl 4-((6-(difluoromethyl)pyridin-3-yl)methoxy)-3-methoxybenzylcarbamate

HRID 706522Notes

Reaction equation

HRID 706522 reaction equation
[OH:1][C:2]1[CH:16]=[CH:15][C:5]([CH2:6][NH:7][C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[CH:4][C:3]=1[O:17][CH3:18].C(=O)([O-])[O-].[K+].[K+].Cl.Cl[CH2:27][C:28]1[CH:29]=[CH:30][C:31]([CH:34]([F:36])[F:35])=[N:32][CH:33]=1>C(#N)C.O>[F:35][CH:34]([F:36])[C:31]1[N:32]=[CH:33][C:28]([CH2:27][O:1][C:2]2[CH:16]=[CH:15][C:5]([CH2:6][NH:7][C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[CH:4][C:3]=2[O:17][CH3:18])=[CH:29][CH:30]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 15713917HCID 15713917, compoundHCID 1181139635-(Chloromethyl)-2-(difluoromethyl)pyridine hydrochloride

Product 1

HCID 118114378Tert-butyl 4-((6-(difluoromethyl)pyridin-3-yl)methoxy)-3-methoxybenzylcarbamateYield 105.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of tert-butyl 4-hydroxy-3-methoxybenzylcarbamate (4.70 g, 18.56 mmol) and potassium carbonate (7.64 g, 55.28 mmol) in acetonitrile (50 mL) was added 5-(chloromethyl)-2-(difluoromethyl)pyridine hydrochloride (4.58 g, 21.40 mmol). The mixture was heated to reflux. After 3 h, the off-white suspension was allowed to cool to room temperature and was diluted with water (200 mL). The mixture was extracted with dichloromethane (3×75 mL). The combined organic phases were dried over magnesium sulfate, filtered, and concentrated to provide 7.74 g (>100%) of tert-butyl 4-((6-(difluoromethyl)pyridin-3-yl)methoxy)-3-methoxybenzylcarbamate as a waxy yellow solid.

Workup

  1. temperatureThe mixture was heated to reflux
  2. extractionThe mixture was extracted with dichloromethane (3×75 mL)
  3. dry with materialThe combined organic phases were dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-4bc9366eec9b49c9b243522e95298e89
Source dataset
uspto-grants-2015_11
Patent number
US09174986B2

Reaction notes

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