Methyl 2,4-Difluorobenzoate → Methyl 2-(6-(benzyloxy)pyridin-3-yloxy)-4-fluorobenzoate

HRID 624393Notes

Reaction equation

HRID 624393 reaction equation
[CH2:1]([O:8][C:9]1[N:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(C)([O-])C.[K+].F[C:23]1[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:24]=1[C:25]([O:27][CH3:28])=[O:26]>CC1CCCO1.C(OCC)(=O)C>[CH2:1]([O:8][C:9]1[N:14]=[CH:13][C:12]([O:15][C:23]2[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:24]=2[C:25]([O:27][CH3:28])=[O:26])=[CH:11][CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 2782897Methyl 2,4-DifluorobenzoateHCID 23665647Potassium tert-butoxideHCID 425530416-(Benzyloxy)pyridin-3-ol

Product 1

HCID 67228431Methyl 2-(6-(benzyloxy)pyridin-3-yloxy)-4-fluorobenzoate

Reagents, catalysts & solvents 2

HCID 73012-MethyltetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
75 °C

Procedure

To 6-(benzyloxy)pyridin-3-ol (1.10 g) in 2-methyltetrahydrofuran (20 mL) was added potassium t-butoxide (5.47 mL, 1.0M in tetrahydrofuran). After stirring for 15 minutes, methyl 2,4-difluorobenzoate (1.035 g) in 2-methyltetrahydrofuran (2 mL) was added and the reaction heated to 75° C. for 1 hour. The reaction was cooled, diluted with ethyl acetate (150 mL), washed with water (50 mL), brine (50 mL), dried over magnesium sulfate, filtered and concentrated. Silica gel chromatography (SF40-80 g) eluting with a gradient of 5% to 20% ethyl acetate/hexanes gave the title compound.

Workup

  1. temperatureThe reaction was cooled
  2. washwashed with water (50 mL), brine (50 mL)
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. washSilica gel chromatography (SF40-80 g) eluting with a gradient of 5% to 20% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-75b847cf353f4de0b04265aa3c78dc54
Source dataset
uspto-grants-2016_04
Patent number
US09303025B2

Reaction notes

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