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

HRID 1778948Notes

Reaction equation

HRID 1778948 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 dioxane (30 mL) followed by 3 M aqueous Na2CO3 (4.93 mL, 14.8 mmol). The resulting mixture was degassed with a stream of nitrogen for 10 minutes then heated at reflux for 16 hours. On cooling, EtOAc (150 mL) was added and the resulting mixture was washed with water (3×50 mL) and brine (50 mL). The organics were dried (Na2SO4), filtered and concentrated under reduced pressure to give a brown solid that was purified by silica gel column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-30% EtOAc in petroleum benzine 40-60° C.) to give the title compound I5 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 a stream of nitrogen for 10 minutes
  2. temperaturethen heated
  3. temperatureat reflux for 16 hours
  4. temperatureOn cooling
  5. additionEtOAc (150 mL) was added
  6. washthe resulting mixture was washed with water (3×50 mL) and brine (50 mL)
  7. dry with materialThe organics were dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customto give a brown solid that
  11. customwas purified by silica gel column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-30% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-0366719df19d4e588bbdd6a58a1c57cc
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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