Cesium carbonate → tert-Butyl 2-methyl-1H-pyrrolo[2,3-b]pyridine-3-carboxylate

HRID 2206555Notes

Reaction equation

HRID 2206555 reaction equation
C([N:4]([C:8]1[C:13](Br)=[CH:12][CH:11]=[CH:10][N:9]=1)C(=O)C)(=O)C.N1CCC[C@H]1C(O)=O.C(=O)([O-])[O-].[Cs+].[Cs+].[C:29]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])(=[O:34])[CH2:30][C:31]([CH3:33])=O>[Cu]I.O1CCOCC1>[CH3:33][C:31]1[NH:4][C:8]2=[N:9][CH:10]=[CH:11][CH:12]=[C:13]2[C:30]=1[C:29]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 15538Tert-butyl acetoacetateHCID 145742L-ProlineHCID 89740773N-acetyl-N-(3-bromopyridin-2-yl)acetamide

Product 1

HCID 89739113tert-Butyl 2-methyl-1H-pyrrolo[2,3-b]pyridine-3-carboxylateYield 20.2%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

To a 5×00 mL round-bottom flask that contains N-acetyl-N-(3-bromopyridin-2-yl)acetamide (14.815 g, 57.6 mmol), was added copper(I) iodide (1.098 g, 5.76 mmol), L-proline (1.327 g, 11.53 mmol), cesium carbonate (28.2 g, 86 mmol), then t-butyl acetoacetate (11.47 ml, 69.2 mmol) and dioxane (100 mL). The reaction was vac/purged with N2 3× then fitted with a septum and a N2 inlet and heated overnight at 70° C. The inorganic solids were removed by filtration over celite and the cake was washed with 100 mL EtOAc. This solution was concentrated and the residue was partitioned between 250 mL brine and 250 mL EtOAc. The aq. Layer was further extracted with EtOAc (2×250 mL) and the combined organic layer was dried over Na2SO4, filtered, concentrated and purified by CC using 1:1 EtOAc:Hex as eluent to provide (2.7 g, 20.2%) of tert-butyl 2-methyl-1H-pyrrolo[2,3-b]pyridine-3-carboxylate. LRMS (M+H+) m/z: calc'd 233.28. found 233.1.

Workup

  1. customThe reaction was vac/purged with N2 3×
  2. customthen fitted with a septum and a N2 inlet
  3. customThe inorganic solids were removed by filtration over celite
  4. washthe cake was washed with 100 mL EtOAc
  5. concentrationThis solution was concentrated
  6. customthe residue was partitioned between 250 mL brine and 250 mL EtOAc
  7. extractionThe aq. Layer was further extracted with EtOAc (2×250 mL)
  8. dry with materialthe combined organic layer was dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. custompurified by CC

Sources & evidence

ORD record
ord-1d01f3c3555d4237b47d1de86aacc4bf
Source dataset
uspto-grants-2016_06
Patent number
US09371331B2

Reaction notes

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