Cesium carbonate → tert-Butyl 6-nitro-3',6'-dihydro-[3,4'-bipyridine]-1'(2'H)-carboxylate

HRID 449617Notes

Reaction equation

HRID 449617 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([N+:8]([O-:10])=[O:9])=[N:6][CH:7]=1.CC1(C)C(C)(C)OB([C:19]2[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH:20]=2)O1.O1CCOCC1.C([O-])([O-])=O.[Cs+].[Cs+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[N+:8]([C:5]1[N:6]=[CH:7][C:2]([C:19]2[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH:20]=2)=[CH:3][CH:4]=1)([O-:10])=[O:9]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 8176205-Bromo-2-nitropyridineHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylate

Product 1

HCID 49840377tert-Butyl 6-nitro-3',6'-dihydro-[3,4'-bipyridine]-1'(2'H)-carboxylateYield 69%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent2×

Conditions

Temperature
80 °C

Procedure

In a 50 mL round-bottomed flask, 5-bromo-2-nitropyridine (3.28 g, 16.2 mmol, Eq: 1) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (5 g, 16.2 mmol, Eq: 1.00) were combined with dioxane (80.0 ml) to give a light yellow solution. Cs2CO3 (10.5 g, 32.3 mmol, Eq: 2) and 3 mL H2O were added. The solution was degassed with Ar before bis(triphenylphosphine)palladium(ii) dichloride (1.13 g, 1.62 mmol, Eq: 0.1) was added. The reaction mixture was heated to 80° C. and stirred for 15 h. The reaction mixture was poured into 300 mL H2O and extracted with EtOAc (3×100 mL). The combined organic extracts were washed with brine and dried over MgSO4. The crude reaction mixture was concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 220 g, 10% to 100% EtOAc/Hex gradient) to give a dark brown impure solid. The solid was triturated with Et2O to afford tert-butyl 4-(6-nitropyridin-3-yl)-5,6-dihydropyridine-1(2H)-carboxylate (685 mg, 69%) as a tan solid. LC/MS-ESI observed [M+H]+ 306.

Workup

  1. customto give a light yellow solution
  2. additionwas added
  3. extractionextracted with EtOAc (3×100 mL)
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over MgSO4
  6. customThe crude reaction mixture
  7. concentrationwas concentrated in vacuo
  8. customThe crude material was purified by flash chromatography (silica gel, 220 g, 10% to 100% EtOAc/Hex gradient)
  9. customto give a dark brown impure solid
  10. customThe solid was triturated with Et2O

Sources & evidence

ORD record
ord-6afd5bd48e5f4d74b4623e6467d36094
Source dataset
uspto-grants-2013_07
Patent number
US08481540B2

Reaction notes

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