Nitrogen → N-(5-ethenyl-2-nitrophenyl)-1-(tetrahydro-2H-pyran-4-yl)-4-piperidinamine

HRID 2064062Notes

Reaction equation

HRID 2064062 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([N+:21]([O-:23])=[O:22])=[C:6]([NH:8][CH:9]2[CH2:14][CH2:13][N:12]([CH:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)[CH2:11][CH2:10]2)[CH:7]=1.[CH:24]([Sn](CCCC)(CCCC)CCCC)=[CH2:25].N#N.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[CH:24]([C:2]1[CH:3]=[CH:4][C:5]([N+:21]([O-:23])=[O:22])=[C:6]([NH:8][CH:9]2[CH2:14][CH2:13][N:12]([CH:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)[CH2:11][CH2:10]2)[CH:7]=1)=[CH2:25]

Participants

7

Reactant 4

HCID 947NitrogenHCID 11776TriphenylphosphineHCID 81998TributylvinyltinHCID 59863010N-(5-bromo-2-nitrophenyl)-1-(tetrahydro-2H-pyran-4-yl)-4-piperidinamine

Product 1

HCID 59863033N-(5-ethenyl-2-nitrophenyl)-1-(tetrahydro-2H-pyran-4-yl)-4-piperidinamineYield 67%

Reagents, catalysts & solvents 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
130 °C

Procedure

To a mixture of N-(5-bromo-2-nitrophenyl)-1-(tetrahydro-2H-pyran-4-yl)-4-piperidinamine D24 (1.8 g, 0.0047 mol) and vinyl tri(n-butyl)tin (1.58 mL, 0.0054 mol) in toluene (70 mL) was added, under a positive flow of N2, triphenyl phosphine (0.295 g, 1.125 mmol) and bis(dibenzylidene acetone)palladium (0) (0.338 g, 0.675 mmol). The mixture was put under a N2 atmosphere and heated at 130° C. for 1.5 hours (LC/MS was used to monitor the reaction). After the reaction was completed the reaction mixture was cooled to room temperature, filtered through a celite pad, and washed with dichloromethane. The filtrate was washed with 10% of aqueous NH4OH solution (3×50 mL), H2O (3×50 mL), and dried with Na2SO4, and concentrated in vacuo. The resulting residue was redissolved in acetonitrile. 416 mg of the title compound was crystallized out and the resulted solution was purified by using a Gilson preparative HPLC system with a Waters Xterra (C-18) column 100 mm by 50 mm ID, eluting with 10% B to 90% B in 10 min, where A=H2O and B=CH3CN pumped at 150 mL/min to yield additional 578 mg of the title compound (overall 994 mg, 67% yield). MS (ESI): 332 [M+H]+; 1H NMR (400 MHz, CDCl3): δ 1.67 (6H, m), 2.11 (2H, d), 2.47 (3H, m), 2.90 (2H, m), 3.39 (2H, t), 3.61 (1H, m), 4.03 (2H, dd), 5.47 (1H, d), 5.88 (1H, d), 6.66 (1H, dd), 6.75 (2H, m), 8.14 (1H, d), 8.23 (1H, d).

Workup

  1. customthe reaction)
  2. temperaturewas cooled to room temperature
  3. filtrationfiltered through a celite pad
  4. washwashed with dichloromethane
  5. washThe filtrate was washed with 10% of aqueous NH4OH solution (3×50 mL), H2O (3×50 mL)
  6. dry with materialdried with Na2SO4
  7. concentrationconcentrated in vacuo
  8. dissolutionThe resulting residue was redissolved in acetonitrile
  9. custom416 mg of the title compound was crystallized out
  10. customthe resulted solution was purified
  11. washeluting with 10% B to 90% B in 10 min

Sources & evidence

ORD record
ord-0b4a083b58f343eca6f2f0c528ed669a
Source dataset
uspto-grants-2012_10
Patent number
US08288413B2

Reaction notes

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