Potassium Carbonate → Methyl 5-(difluoromethoxy)picolinate

HRID 1911027Notes

Reaction equation

HRID 1911027 reaction equation
Cl.[OH:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]([O:11][CH3:12])=[O:10])=[N:7][CH:8]=1.C(=O)([O-])[O-].[K+].[K+].Cl[C:20]([F:30])([F:29])C(C1C=CC=CC=1)=O>O.C(#N)C>[F:29][CH:20]([F:30])[O:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]([O:11][CH3:12])=[O:10])=[N:7][CH:8]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 2382962-Chloro-2,2-difluoroacetophenoneHCID 67086052HCID 67086052, compound

Product 1

HCID 57827732Methyl 5-(difluoromethoxy)picolinateYield 61%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of methyl 5-hydroxypicolinate hydrochloride from step K1 (1.12 g, 5.91 mmol), potassium carbonate (8.16 g, 59.1 mmol) and α-chloro-α,α-difluoroacetophenone (3.92 mL, 26.6 mmol) in water (20 mL) and acetonitrile (20 mL) was stirred at 75° C. for 5 h. The solid was filtered out and washed with diethyl ether. The filtrate was washed with water and concentrated. The residue was purified using silica gel column chromatography (hexanes-50% EtOAc) to give methyl 5-(difluoromethoxy)picolinate (730 mg, 3.59 mmol, 61% yield). 1H NMR (500 HMz, chloroform-d) δ 8.60 (d, J=2.4 Hz, 1H), 8.20 (dd, J=8.6, 0.5 Hz, 1H), 7.62 (dd, J=8.7, 2.7 Hz, 1H), 6.81-6.49 (m, 1H), 4.03 (s, 3H).

Workup

  1. filtrationThe solid was filtered out
  2. washwashed with diethyl ether
  3. washThe filtrate was washed with water
  4. concentrationconcentrated
  5. customThe residue was purified

Sources & evidence

ORD record
ord-d0b6921d41ac470ab44d0feca8738a91
Source dataset
uspto-grants-2013_12
Patent number
US08604024B2

Reaction notes

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