Toluene → N-(tert-butoxycarbonyl)piperidine

HRID 2042564Notes

Reaction equation

HRID 2042564 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-48b3d4309f0e4938a52022455a1267e0
Source dataset
uspto-grants-2013_11
Patent number
US08586588B2

Reaction notes

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