4-Nitrophenol → 4-(4-Nitrophenoxy)piperidine

HRID 2111833Notes

Reaction equation

HRID 2111833 reaction equation
C([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1)(OC(C)(C)C)=O.[N+:15]([C:18]1[CH:23]=[CH:22][C:21](O)=[CH:20][CH:19]=1)([O-:17])=[O:16].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1>[N+:15]([C:18]1[CH:23]=[CH:22][C:21]([O:14][CH:11]2[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]2)=[CH:20][CH:19]=1)([O-:17])=[O:16]

Participants

6

Reactant 4

HCID 9804-NitrophenolHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylate

Product 1

HCID 219186534-(4-Nitrophenoxy)piperidine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

N-Boc-4-piperidinol (10 g, 50 mmol), 4-nitrophenol (7.0 g, 50 mmol) and triphenylphosphine (15.7 g, 60 mmol) were dissolved in dry tetrahydrofuran (150 mL), and cooled on the ice bath. Diisopropyl azodicarboxylate (11.8 mL, 60 mmol) was added slowly, and stirred for 2 days at room temperature. The solvent was distilled off under reduced pressure, diethyl ether was added, and the solid precipitate was filtered off. The filtrate was concentrated and the product was purified by silica gel column chromatography (hexane/ethyl acetate=6/1). Trifluoroacetic acid was added to the obtained residue and stirred at room temperature for 1 hour. After distillation under reduced pressure, 1N sodium hydroxide aqueous solution was added, and the mixture extracted with ethyl acetate. After drying with anhydrous sodium sulfate, the product was concentrated and dried to obtain the target substance (6.75 g, 61%).

Workup

  1. distillationThe solvent was distilled off under reduced pressure, diethyl ether
  2. additionwas added
  3. filtrationthe solid precipitate was filtered off
  4. concentrationThe filtrate was concentrated
  5. customthe product was purified by silica gel column chromatography (hexane/ethyl acetate=6/1)
  6. additionTrifluoroacetic acid was added to the obtained residue
  7. stirringstirred at room temperature for 1 hour
  8. distillationAfter distillation under reduced pressure, 1N sodium hydroxide aqueous solution
  9. additionwas added
  10. extractionthe mixture extracted with ethyl acetate
  11. dry with materialAfter drying with anhydrous sodium sulfate
  12. concentrationthe product was concentrated
  13. customdried
  14. customto obtain the target substance (6.75 g, 61%)

Sources & evidence

ORD record
ord-190edd83b8d34853bad24351267f49db
Source dataset
uspto-grants-2009_04
Patent number
US07521455B2

Reaction notes

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