Sodium Carbonate → 5-Nitro-3',6'-dihydro-2'H-[2,4]bipyridinyl-1'-carboxylic acid tert-butyl ester

HRID 592346Notes

Reaction equation

HRID 592346 reaction equation
[C:1]([N:8]1[CH2:13][CH:12]=[C:11](B2OC(C)(C)C(C)(C)O2)[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].Br[C:24]1[CH:29]=[CH:28][C:27]([N+:30]([O-:32])=[O:31])=[CH:26][N:25]=1.C(=O)([O-])[O-].[Na+].[Na+]>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.O1CCOCC1>[N+:30]([C:27]1[CH:28]=[CH:29][C:24]([C:11]2[CH2:10][CH2:9][N:8]([C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2])[CH2:13][CH:12]=2)=[N:25][CH:26]=1)([O-:32])=[O:31]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 782402-Bromo-5-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 591285695-Nitro-3',6'-dihydro-2'H-[2,4]bipyridinyl-1'-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a mixture of N-Boc-1,2,3,6-tetrahydropyridine-4-boronic acid pinacol ester (1.52 g, 4.93 mmol), 2-bromo-5-nitropyridine (1.00 g, 4.93 mmol) and PdCl2(PPh3)2 (173 mg, 0.246 mmol) under nitrogen was added 1,4-dioxane (30 mL) followed by 3 M aqueous sodium carbonate (4.93 mL, 14.8 mmol). The resulting mixture was degassed with nitrogen for 10 minutes then heated at reflux for 16 hours. On cooling EtOAc (150 mL) was added and the resulting solution was washed with water (3×50 mL), brine (50 mL) then dried (Na2SO4). The volatiles were evaporated under reduced pressure to give a brown solid that was purified using silica gel column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-30% EtOAc in petroleum benzine 40-60° C.) to give the title compound I8 as a yellow solid (1.43 g, 95%); 1H NMR (400 MHz, CDCl3) δ 9.37 (dd, J=2.6, 0.5 Hz, 1H), 8.43 (dd, J=8.8, 2.7 Hz, 1H), 7.53 (d, J=8.8 Hz, 1H), 6.95-6.83 (m, 1H), 4.20 (d, J=3.0 Hz, 2H), 3.67 (t, J=5.6 Hz, 2H), 2.70-2.63 (m, 2H), 1.49 (s, 9H). LCMS-A: rt 6.140 min; m/z 304 [M−H]−.

Workup

  1. customThe resulting mixture was degassed with nitrogen for 10 minutes
  2. temperaturethen heated
  3. temperatureat reflux for 16 hours
  4. temperatureOn cooling EtOAc (150 mL)
  5. additionwas added
  6. washthe resulting solution was washed with water (3×50 mL), brine (50 mL)
  7. dry with materialthen dried (Na2SO4)
  8. customThe volatiles were evaporated under reduced pressure
  9. customto give a brown solid that
  10. customwas purified
  11. customsilica gel column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-30% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-cd9f9efbb61b4fb68833edd46f66653b
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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