Dimethylformamide → Methyl 2-(5-bromopyridin-3-yloxy)-4-fluorobenzoate

HRID 573105Notes

Reaction equation

HRID 573105 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[N:6][CH:7]=1.CC(C)([O-])C.[K+].F[C:16]1[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:17]=1[C:18]([O:20][CH3:21])=[O:19].CN(C)C=O>CC1CCCO1.C(OCC)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]([O:8][C:16]2[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:17]=2[C:18]([O:20][CH3:21])=[O:19])[CH:5]=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 5995293-Bromo-5-hydroxypyridineHCID 2782897Methyl 2,4-DifluorobenzoateHCID 23665647Potassium tert-butoxide

Product 1

HCID 67227657Methyl 2-(5-bromopyridin-3-yloxy)-4-fluorobenzoate

Reagents, catalysts & solvents 2

HCID 73012-MethyltetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of 5-bromopyridin-3-ol (1.060 g) in 2-methyltetrahydrofuran (15 mL) was added potassium tert-butoxide (6.09 mL, 1.0M in tetrahydrofuran) dropwise. After stirring for 5 minutes, methyl 2,4-difluorobenzoate (1.049 g) was added as a solution in 2-methyltetrahydrofuran (2 mL) and the reaction was heated to 75° C. N,N-Dimethylformamide (2 mL) was added to the reaction and the reaction was stirred overnight. The reaction was cooled, diluted with ethyl acetate (100 mL) and washed with water (50 mL), brine (50 mL), dried over magnesium sulfate, filtered, and concentrated. Silica gel chromatography (SF40-80) eluting with a gradient of 5% to 35% ethyl acetate/hexanes gave the product.

Workup

  1. stirringthe reaction was stirred overnight
  2. temperatureThe reaction was cooled
  3. washwashed with water (50 mL), brine (50 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. washSilica gel chromatography (SF40-80) eluting with a gradient of 5% to 35% ethyl acetate/hexanes
  8. customgave the product

Sources & evidence

ORD record
ord-4d177645839a45b0823d1cea560f7a46
Source dataset
uspto-grants-2015_05
Patent number
US09029404B2

Reaction notes

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