Toluene → N-(tert-butoxycarbonyl)piperidine

HRID 1186853Notes

Reaction equation

HRID 1186853 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O.C1(C)C=CC=CC=1.OC1C=CC(CC(=O)C)=CC=1.[C:50]([O:54][C:55]([N:57]1[CH2:62][CH2:61][CH:60](O)[CH2:59][CH2:58]1)=[O:56])([CH3:53])([CH3:52])[CH3:51]>O1CCCC1>[C:50]([O:54][C:55]([N:57]1[CH2:62][CH2:61][CH2:60][CH2:59][CH2:58]1)=[O:56])([CH3:53])([CH3:51])[CH3:52]

Participants

7

Reactant 5

HCID 1140TolueneHCID 11776TriphenylphosphineHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 5462977Diethyl azodicarboxylateHCID 70192744-Hydroxyphenylacetone

Product 1

HCID 7010304N-(tert-butoxycarbonyl)piperidineYield 86.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of triphenylphosphine (18.5 g, 70.6 mmol) and 40% DEAD in toluene (12.3 g, 70.6 mmol) in 125.0 mL of tetrahydrofuran was cooled to 0° C. under N2 as a solution of 1-(4-hydroxy-phenyl)-propan-2-one (6.54 g, 43.6 mmol) and 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (10.7 g, 53.2 mmol) in 125.0 mL of tetrahydrofuran was added dropwise via addition funnel After stirred at rt overnight, the solvent was evaporated. The residue was stirred in hexane/EtOAc, the solid formed was filtered. The hexane/EtOAC solution was concentrated and purified by ISCO graduate chromatography (hexane-20% EtOAc in hexane) to give 4-[4-2-oxo-propyl)-phenoxy]-piperidine-1-carboxylic acid tert-butyl ester (8.52 g, 59%).

Workup

  1. additionwas added dropwise via addition funnel
  2. customthe solvent was evaporated
  3. stirringThe residue was stirred in hexane/EtOAc
  4. customthe solid formed
  5. filtrationwas filtered
  6. concentrationThe hexane/EtOAC solution was concentrated
  7. custompurified by ISCO graduate chromatography (hexane-20% EtOAc in hexane)

Sources & evidence

ORD record
ord-579f9a63e61d478898f05330be9466f2
Source dataset
uspto-grants-2014_03
Patent number
US08673916B2

Reaction notes

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