Dimethylformamide → Methyl 2-(6-chloro-5-fluoropyridin-3-yloxy)-4-fluorobenzoate

HRID 573112

Reaction equation

HRID 573112 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[F:9].CC([O-])(C)C.[K+].F[C:17]1[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:18]=1[C:19]([O:21][CH3:22])=[O:20].CN(C)C=O>CC1CCCO1.C(OCC)(=O)C>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([O:8][C:17]2[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:18]=2[C:19]([O:21][CH3:22])=[O:20])=[CH:4][C:3]=1[F:9]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 2782897Methyl 2,4-DifluorobenzoateHCID 23665647Potassium tert-butoxideHCID 404247372-Chloro-3-fluoro-5-hydroxypyridine

Product 1

HCID 86642876Methyl 2-(6-chloro-5-fluoropyridin-3-yloxy)-4-fluorobenzoate

Reagents, catalysts & solvents 2

HCID 73012-MethyltetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 6-chloro-5-fluoropyridin-3-ol (0.977 g) in 2-methyltetrahydrofuran (12 mL) was added potassium 2-methylpropan-2-olate (1.0M in tetrahydrofuran, 7.28 mL). After stirring for 15 minutes at room temperature, methyl 2,4-difluorobenzoate (1.710 g) was added as a solution in 2-methyltetrahydrofuran (2 mL) followed by N,N-dimethylformamide (2 mL) then the reaction was heated to 75° C. under a nitrogen atmosphere. After stirring overnight the reaction was cooled, diluted with ethyl acetate (100 mL) and washed with water (50 mL) and brine (50 mL), dried over magnesium sulfate, filtered, and concentrated. Silica gel chromatography (GraceResolv 40 g) eluting with a gradient of 2% to 15% ethyl acetate/hexanes gave the title compound.

Workup

  1. temperaturethe reaction was heated to 75° C. under a nitrogen atmosphere
  2. stirringAfter stirring overnight the reaction
  3. temperaturewas cooled
  4. washwashed with water (50 mL) and brine (50 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. washSilica gel chromatography (GraceResolv 40 g) eluting with a gradient of 2% to 15% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-83abc5fa911a4bf9b6f6b3b079582642
Source dataset
uspto-grants-2015_05
Patent number
US09029404B2

Linked notes

Loading…