Water → Tert-butyl 4-(3-nitrophenyl)-1,2,3,6-tetrahydropyridine-1-carboxylate

HRID 472472Notes

Reaction equation

HRID 472472 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Br[C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([N+:27]([O-:29])=[O:28])[CH:22]=1.[C:30]([O:34][C:35]([N:37]1[CH2:42][CH:41]=[C:40](B2OC(C)(C)C(C)(C)O2)[CH2:39][CH2:38]1)=[O:36])([CH3:33])([CH3:32])[CH3:31].C(=O)([O-])[O-].[Na+].[Na+].O>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[C:30]([O:34][C:35]([N:37]1[CH2:38][CH:39]=[C:40]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([N+:27]([O-:29])=[O:28])[CH:22]=2)[CH2:41][CH2:42]1)=[O:36])([CH3:33])([CH3:31])[CH3:32]

Participants

8

Reactant 5

HCID 962WaterHCID 10340Sodium CarbonateHCID 11457Benzene, 1-bromo-3-nitro-HCID 11776TriphenylphosphineHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylate

Product 1

HCID 15751429Tert-butyl 4-(3-nitrophenyl)-1,2,3,6-tetrahydropyridine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a round bottom flask was added palladium acetate (0.49 g, 2.2 mmol), triphenylphosphine (2.38 g, 9.06 mmol) and 1,4-dioxane (40 mL). The mixture was stirred for 15 minutes under an atmosphere of nitrogen until a bright yellow suspension resulted. 1-Bromo-3-nitro-benzene (3.0 g, 15 mmol), 4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (5.0 g, 16 mmol) and 1.50 M of sodium carbonate in water (24.5 mL, 36.8 mmol) were added. The mixture was stirred and heated at 80° C. for 24 hours. The mixture was cooled to room temperature and the volatiles were evaporated under reduced pressure. To the residue was added water (100 mL) then extracted with dichloromethane (3×50 mL). The combined organic layers were washed with water (2×50 mL) and saturated aqueous sodium chloride (50 mL), dried over magnesium sulfate, filtered and evaporated. The residue was purified via chromatography using an ISCO automated purification apparatus (silica gel column 80 g 5%→25% ethyl acetate:hexane solvent gradient). 4-(3-Nitro-phenyl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester was isolated as a yellow oil (3.95 g, 88%). 1H NMR (400 MHz, CDCl3, δ, ppm): 8.23 (s, 1H), 8.11 (d, J=8.1 Hz, 1H), 7.69 (d, J=7.7 Hz, 1H), 7.51 (t, J=7.8 Hz, 1H), 6.20 (br s, 1H), 4.12 (s, 2H), 3.70-3.65 (m, 2H), 2.56 (s, 2H), 1.50 (s, 9H).

Workup

  1. customresulted
  2. stirringThe mixture was stirred
  3. temperatureThe mixture was cooled to room temperature
  4. customthe volatiles were evaporated under reduced pressure
  5. additionTo the residue was added water (100 mL)
  6. extractionthen extracted with dichloromethane (3×50 mL)
  7. washThe combined organic layers were washed with water (2×50 mL) and saturated aqueous sodium chloride (50 mL)
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. customevaporated
  11. customThe residue was purified via chromatography
  12. custompurification apparatus (silica gel column 80 g 5%→25% ethyl acetate:hexane solvent gradient)

Sources & evidence

ORD record
ord-929ac2da93c1426391cb433302f84bb8
Source dataset
uspto-grants-2014_01
Patent number
US08633173B2

Reaction notes

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