Cesium carbonate → 1-[4-Nitro-3-(propan-2-yloxy)phenyl]piperidin-4-yl acetate

HRID 518816Notes

Reaction equation

HRID 518816 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[C:4]([O:11][CH:12]([CH3:14])[CH3:13])[CH:3]=1.[C:15]([O:18][CH:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1)(=[O:17])[CH3:16].C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1>O1CCOCC1.C(OCC)(=O)C.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:15]([O:18][CH:19]1[CH2:24][CH2:23][N:22]([C:2]2[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[C:4]([O:11][CH:12]([CH3:14])[CH3:13])[CH:3]=2)[CH2:21][CH2:20]1)(=[O:17])[CH3:16]

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 11252075Piperidin-4-yl acetateHCID 226243214-Bromo-2-isopropoxy-1-nitro-benzene

Product 1

HCID 866979841-[4-Nitro-3-(propan-2-yloxy)phenyl]piperidin-4-yl acetateYield 42.8%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 1 g of 4-bromo-1-nitro-2-(propan-2-yloxy)benzene, 1.19 g of piperidin-4-yl acetate, 5.01 g of caesium carbonate, 86 mg of palladium acetate and 334 mg of 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene, in 50 ml of dioxane, is refluxed for 3 hours. The mixture is diluted with ethyl acetate and water. The aqueous phase is extracted with ethyl acetate (2×). The combined organic phases are dried over magnesium sulfate and concentrated under vacuum. The residue is purified on silica, elution being carried out with cyclohexane/ethyl acetate (80/80 to 50/50), so as to give 530 mg 1-[4-nitro-3-(propan-2-yloxy)phenyl]piperidin-4-yl acetate in the form of a brown solid.

Workup

  1. extractionThe aqueous phase is extracted with ethyl acetate (2×)
  2. dry with materialThe combined organic phases are dried over magnesium sulfate
  3. concentrationconcentrated under vacuum
  4. customThe residue is purified on silica, elution

Sources & evidence

ORD record
ord-5daf20321b0d4519b620b7eec465cbe1
Source dataset
uspto-grants-2015_08
Patent number
US09115140B2

Reaction notes

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