Cesium carbonate → 5-(Benzyloxy)-3-methyl-2-(propan-2-yloxy)pyridine-4-carboxylic acid

HRID 577581Notes

Reaction equation

HRID 577581 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([C:17]([O:19]C2C=CC=CC=2)=[O:18])=[C:11]([CH3:16])[C:12](Br)=[N:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=[O:27].[Cs+].[Cs+].[CH3:32][C:33](P(C(C)(C)C)C1N(C2C(C3C=CC=CC=3)=NN(C3C=CC=CC=3)C=2C2C=CC=CC=2)N=CC=1)([CH3:35])C.[OH-].[Na+]>CC(O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CO>[CH2:1]([O:8][C:9]1[C:10]([C:17]([OH:19])=[O:18])=[C:11]([CH3:16])[C:12]([O:27][CH:33]([CH3:35])[CH3:32])=[N:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 14798Sodium HydroxideHCID 11547931BippyPhosHCID 51350422Phenyl 5-(benzyloxy)-2-bromo-3-methylpyridine-4-carboxylate

Product 1

HCID 867238085-(Benzyloxy)-3-methyl-2-(propan-2-yloxy)pyridine-4-carboxylic acidYield 553.1%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 887MethanolSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
115 °C

Procedure

A suspension of phenyl 5-(benzyloxy)-2-bromo-3-methylpyridine-4-carboxylate (2.4 g, 6.0 mmol) and Cs2CO3 (6.1 g, 19 mmol) in i-PrOH (36 mL) was degassed with N2 for 2 minutes. To the reaction mixture was added Pd2(dba)3 (0.31 g, 0.34 mmol) and t-Bu-BippyPhos (0.34 g, 0.66 mmol, cas:894086-00-1). The mixture was heated in the microwave at 115° C. for 1 hour. To the reaction mixture was added 4M NaOH (7 mL) and MeOH (7 mL) and the reaction mixture was stirred at 60° C. for 3 hours. The reaction mixture was concentrated under vacuum. To the residue was added EtOAc (60 mL) and H2O (80 mL). The aqueous layer was acidified with conc. HCl to pH 4 and extracted with EtOAc (2×40 mL). The combined organic layers were washed with brine (60 mL), dried over Na2SO4, and concentrated under vacuum to give 5-(benzyloxy)-3-methyl-2-(propan-2-yloxy)pyridine-4-carboxylic acid (131a, 1.1 g, 60%) as a yellow solid.

Workup

  1. customwas degassed with N2 for 2 minutes
  2. concentrationThe reaction mixture was concentrated under vacuum
  3. additionTo the residue was added EtOAc (60 mL) and H2O (80 mL)
  4. extractionextracted with EtOAc (2×40 mL)
  5. washThe combined organic layers were washed with brine (60 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-03d4c906b30a4751a9c8011e65bb642a
Source dataset
uspto-grants-2015_05
Patent number
US09040515B2

Reaction notes

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