Potassium Carbonate → tert-butyl 3-(6-aminopyridin-3-yl)-2,5-dihydro-1H-pyrrole-1-carboxylate

HRID 1431105Notes

Reaction equation

HRID 1431105 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]=[C:10](OS(C(F)(F)F)(=O)=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].CC1(C)C(C)(C)OB([C:35]2[CH:36]=[CH:37][C:38]([NH2:41])=[N:39][CH:40]=2)O1.C([O-])(O)=O.[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]=[C:10]([C:35]2[CH:40]=[N:39][C:38]([NH2:41])=[CH:37][CH:36]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 27565555-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amineHCID 59648037tert-Butyl 3-(((trifluoromethyl)sulfonyl)oxy)-2,5-dihydro-1H-pyrrole-1-carboxylate

Product 1

HCID 66742367tert-butyl 3-(6-aminopyridin-3-yl)-2,5-dihydro-1H-pyrrole-1-carboxylateYield 84%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

In a 25 mL round-bottomed flask, 3-trifluoromethanesulfonyloxy-2,5-dihydro-pyrrole-1-carboxylic acid tert-butyl ester (780 mg, 2.46 mmol, Eq: 1.00) was combined with THF (20 ml) to give a colorless solution. The solution was purged with argon for 10 min. Potassium carbonate (1.72 g, 12.3 mmol, Eq: 5.0), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (649 mg, 2.95 mmol, Eq: 1.20), tetrakis(triphenylphosphine)palladium(0) (28.4 mg, 24.6 μmol, Eq: 0.01) and water (200 μl) were added. The reaction mixture was heated to 70° C. and stirred for 16 h. The reaction mixture was poured into saturated NaHCO3 and extracted twice with Et2O. The organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 40 g, 50% (60:10:1 DCM:MeOH:NH4OH)/DCM) to give 3-(6-amino-pyridin-3-yl)-2,5-dihydro-pyrrole-1-carboxylic acid tert-butyl ester (538 mg, 84%). LC/MS-ESI observed [M+H]+ 262.

Workup

  1. customto give a colorless solution
  2. customThe solution was purged with argon for 10 min
  3. extractionextracted twice with Et2O
  4. washThe organic layer was washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified by flash chromatography (silica gel, 40 g, 50% (60:10:1 DCM:MeOH:NH4OH)/DCM)

Sources & evidence

ORD record
ord-588d92dc295141dd9b9025e313962529
Source dataset
uspto-grants-2015_01
Patent number
US08940741B2

Reaction notes

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