Picolinic acid → 6-(2-Chloro-phenoxy)-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-c]pyridine-1-carboxylic acid tert-butyl ester

HRID 1475403Notes

Reaction equation

HRID 1475403 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[CH:15]=[C:14](Br)[N:13]=[CH:12][C:11]=2[C:10]([CH3:19])([CH3:18])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[OH:27].N1C=CC=CC=1C(O)=O.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CS(C)=O.[Cu]I>[C:1]([O:5][C:6]([N:8]1[C:16]2[CH:15]=[C:14]([O:27][C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=3[Cl:20])[N:13]=[CH:12][C:11]=2[C:10]([CH3:19])([CH3:18])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 1018Picolinic acidHCID 72452-ChlorophenolHCID 62657Potassium Phosphate, TribasicHCID 86724003Tert-butyl 6-bromo-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-C]pyridine-1-carboxylate

Product 1

HCID 709805436-(2-Chloro-phenoxy)-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-c]pyridine-1-carboxylic acid tert-butyl esterYield 82.9%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

A solution of 6-bromo-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-c]pyridine-1-carboxylic acid tert-butyl ester (150 mg, 0.46 mmol), 2-chlorophenol (0.071 mL, 0.69 mmol), CuI (17 mg, 0.046 mmol), picolinic acid (23 mg, 0.092 mmol) and potassium phosphate (195 mg, 0.92 mmol) in DMSO (1 mL) was stirred at 85° C. overnight. The mixture was allowed to cool and then partitioned between EtOAc and water. The organic extract was washed with brine, dried (MgSO4) and evaporated in vacuo. Chromatography (SiO2; gradient elution with 2-10% ethyl acetate in petrol) gave the title compound (143 mg). MS: [M+H]+=375.

Workup

  1. temperatureto cool
  2. custompartitioned between EtOAc and water
  3. extractionThe organic extract
  4. washwas washed with brine
  5. dry with materialdried (MgSO4)
  6. customevaporated in vacuo
  7. washChromatography (SiO2; gradient elution with 2-10% ethyl acetate in petrol)

Sources & evidence

ORD record
ord-388cf3889889497b9429517ff1bb5d84
Source dataset
uspto-grants-2015_04
Patent number
US09018214B2

Reaction notes

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