Tetrahydrofuran → 4-[(1-Methyl-3-piperidinyl)oxy]benzenamine

HRID 1830032Notes

Reaction equation

HRID 1830032 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[K+].C1COCC1.[CH3:16][N:17]1[CH2:22][CH2:21][CH2:20][CH:19]([OH:23])[CH2:18]1.F[C:25]1[CH:30]=[CH:29][C:28]([N+:31]([O-])=O)=[CH:27][CH:26]=1>CCO.[Pd].O>[CH3:16][N:17]1[CH2:22][CH2:21][CH2:20][CH:19]([O:23][C:25]2[CH:30]=[CH:29][C:28]([NH2:31])=[CH:27][CH:26]=2)[CH2:18]1

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 9590p-FluoronitrobenzeneHCID 980163-Piperidinol, 1-methyl-HCID 3251421Potassium bis(trimethylsilyl)amide

Product 1

HCID 220554854-[(1-Methyl-3-piperidinyl)oxy]benzenamine

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Procedure

KHMDS (1.1 equivalent) was added to a THF solution of 1-methylpiperidin-3-ol (1 equivalent) at 0° C. and stirred until H2 evolution ceased. 1-fluoro-4-nitrobenzene (1 equivalent) was then added and the solution was allowed to warm to room temperature. After 2 hours, water was added and the mixture was extracted with EtOAc (3×). The combined organic extracts were dried over Na2SO4, and concentrated in vacuo to give a bright yellow oil which was directly used in the reduction step. The oil (1 equivalent) and a catalytic amount of 10% Pd/C were suspended in anhydrous EtOH at room temperature. The reaction flask was evacuated and subsequently filled with H2. After stirring for 18 hours, the mixture was filtered through Celite, and the solvent was concentrated in vacuo to yield 4-(1-methyl-3-piperidyloxy)phenylamine. LC/MS (m/z) 207.2 (MH+), Rt 0.47 minutes.

Workup

  1. extractionthe mixture was extracted with EtOAc (3×)
  2. dry with materialThe combined organic extracts were dried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customto give a bright yellow oil which
  5. customThe reaction flask was evacuated
  6. additionsubsequently filled with H2
  7. stirringAfter stirring for 18 hours
  8. filtrationthe mixture was filtered through Celite
  9. concentrationthe solvent was concentrated in vacuo

Sources & evidence

ORD record
ord-70510dc3afdc4dafb01e3b3233af75df
Source dataset
uspto-grants-2006_06
Patent number
US07064215B2

Reaction notes

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