Toluene → N-(tert-butoxycarbonyl)piperidine

HRID 887019Notes

Reaction equation

HRID 887019 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-b1634dcbb78b4acda77e6c42de5e752a
Source dataset
uspto-grants-2012_08
Patent number
US08247414B2

Reaction notes

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