Cesium carbonate → (4-Methoxy-3-nitro-phenyl)-methyl-(tetrahydro-pyran-4-yl)-amine

HRID 51896Notes

Reaction equation

HRID 51896 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[C:4]([N+:10]([O-:12])=[O:11])[CH:3]=1.Cl.[CH3:14][NH:15][CH:16]1[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:9][O:8][C:5]1[CH:6]=[CH:7][C:2]([N:15]([CH3:14])[CH:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)=[CH:3][C:4]=1[N+:10]([O-:12])=[O:11]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 1185334-Bromo-2-nitroanisoleHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 22736998N-methyloxan-4-amine hydrochloride

Product 1

HCID 22736985(4-Methoxy-3-nitro-phenyl)-methyl-(tetrahydro-pyran-4-yl)-amineYield 18.5%

Reagents, catalysts & solvents 2

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

Procedure

To a stirred solution of 7.50 g (32.0(mmol) 4-bromo-2-nitro-anisole in 200 ml dioxane were added 6.86 g (45.0 mmol) methyl-(tetrahydro-pyran-4-yl)-amine hydrochloride (1:1), 1.13 g (3.0 mmol) 2-(dicyclohexylphosphino)biphenyl, 14.75 g (45.0 mmol) cesium carbonate, and 360 mg (2.0 mmol) palladium (II) acetate. The mixture was heated at reflux for 72 h and then poured onto water and extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated in vacuo. Flash chromatography (1/2 hexane/ethyl acetate) afforded 1.59 g (18.5%) (4-methoxy-3-nitro-phenyl)-methyl-(tetrahydro-pyran-4-yl)-amine as a red solid. ES-MS m/e (%): 267 (M+H+, 100).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 72 h
  3. additionpoured onto water
  4. extractionextracted three times with ethyl acetate
  5. dry with materialThe combined organic phases were dried over sodium sulfate
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-199bc6f59d1343be94ae985c05fa5fa6
Source dataset
uspto-grants-2004_03
Patent number
US06713499B2

Reaction notes

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