Water → Methyl 6-(difluoromethoxy)picolinate

HRID 594303Notes

Reaction equation

HRID 594303 reaction equation
[O:1]=[C:2]1[NH:7][C:6]([C:8]([O:10][CH3:11])=[O:9])=[CH:5][CH:4]=[CH:3]1.[H-].[Na+].FS([C:18](C(O)=O)([F:20])[F:19])(=O)=O.O>CC#N>[F:19][CH:18]([F:20])[O:1][C:2]1[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 27375162,2-Difluoro-2-(fluorosulfonyl)acetic acidHCID 12342664Methyl 6-oxo-1,6-dihydropyridine-2-carboxylate

Product 1

HCID 69081734Methyl 6-(difluoromethoxy)picolinate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of methyl 6-oxo-1,6-dihydropyridine-2-carboxylate (3.074 g; 20.07 mmol) in anh. MeCN (310 ml) was treated portionwise with NaH (60% dispersion in mineral oil; 2.167 g; 54.19 mmol), and stirring at rt, under nitrogen, was continued for 30 min. FSO2CF2CO2H (6.077 g; 34.12 mmol) was then added dropwise, and the resulting heterogeneous mixture was further stirred at rt, under nitrogen, for 30 min. Water (25 ml) was slowly added, and MeCN was removed under reduced pressure. Water (150 ml) and AcOEt (150 ml) were added, and the separated aq. layer was further extracted with AcOEt (2×100 ml). The mixed organic layers were washed with brine (100 ml), dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by FC (DCM) afforded methyl 6-(difluoromethoxy)picolinate as a yellow solid. LC-MS (conditions D): tR=0.89 min.; no ionisation.

Workup

  1. stirringthe resulting heterogeneous mixture was further stirred at rt, under nitrogen, for 30 min
  2. customMeCN was removed under reduced pressure
  3. additionWater (150 ml) and AcOEt (150 ml) were added
  4. extractionthe separated aq. layer was further extracted with AcOEt (2×100 ml)
  5. washThe mixed organic layers were washed with brine (100 ml)
  6. dry with materialdried over anh. MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated to dryness under reduced pressure
  9. customPurification by FC (DCM)

Sources & evidence

ORD record
ord-dd258f89f22641828a2e81c1feaa1d25
Source dataset
uspto-grants-2016_01
Patent number
US09242970B2

Reaction notes

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