Cesium carbonate → 3-Amino-6-(4-fluoro-phenyl)-5-trifluoromethyl-pyridine-2-carboxylic acid

HRID 444935Notes

Reaction equation

HRID 444935 reaction equation
[NH2:1][C:2]1[C:3]([C:13]([OH:15])=[O:14])=[N:4][C:5](Br)=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[F:16][C:17]1[CH:22]=[CH:21][C:20](B(O)O)=[CH:19][CH:18]=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1COCC1>[NH2:1][C:2]1[C:3]([C:13]([OH:15])=[O:14])=[N:4][C:5]([C:20]2[CH:21]=[CH:22][C:17]([F:16])=[CH:18][CH:19]=2)=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 2856454-Fluorophenylboronic acidHCID 584423503-Amino-6-bromo-5-(trifluoromethyl)picolinic acid2×

Product 1

HCID 584423103-Amino-6-(4-fluoro-phenyl)-5-trifluoromethyl-pyridine-2-carboxylic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture comprising 3-amino-6-bromo-5-trifluoromethyl-pyridine-2-carboxylic acid (Intermediate A) (1 g, 3.51 mmol), 4-fluorophenylboronic acid (0.736 g, 5.26 mmol) and 1,1′Bis(diphenylphosphoshio)ferrocene palladium dichloride (0.286 g, 0.351 mmol) and 1.0M Cs2CO3 (3.3 ml) in THF (10 ml) was heated to reflux for 10 hours. After cooling to RT, the mixture was partitioned between DCM (100 ml) and 1 M NaOH (2×100 ml). The aqueous phase was acidified with 5M HCl and the resulting milky solution was extracted into DCM (2×100 ml). The organic portion was separated, dried (MgSO4) and concentrated in vacuo to afford the product as a crude oil. The crude material was purified by flash chromatography on silica cartridge eluting with a gradient of DCM: MeOH from 0% to 10% MeOH to afford the title product as a pale yellow solid;

Workup

  1. temperatureto reflux for 10 hours
  2. customthe mixture was partitioned between DCM (100 ml) and 1 M NaOH (2×100 ml)
  3. extractionthe resulting milky solution was extracted into DCM (2×100 ml)
  4. customThe organic portion was separated
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customto afford the product as a crude oil
  8. customThe crude material was purified by flash chromatography on silica cartridge
  9. washeluting with a gradient of DCM

Sources & evidence

ORD record
ord-ad1fc2dbe0734ef7bc07b460be15286f
Source dataset
uspto-grants-2013_07
Patent number
US08476269B2

Reaction notes

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