Triphenylphosphine → 1-Boc-4-(3-nitro-5-trifluoromethyl-phenoxy)-piperidine

HRID 2109561Notes

Reaction equation

HRID 2109561 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]([OH:14])[CH:7]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:9]=1)([O-:3])=[O:2].[C:15]([N:22]1[CH2:27][CH2:26][CH:25](O)[CH2:24][CH2:23]1)([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[C:15]([N:22]1[CH2:23][CH2:24][CH:25]([O:14][C:6]2[CH:7]=[C:8]([C:10]([F:11])([F:12])[F:13])[CH:9]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=2)[CH2:26][CH2:27]1)([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 27562513-Hydroxy-5-nitrobenzotrifluorideHCID 5462977Diethyl azodicarboxylate

Product 1

HCID 219596141-Boc-4-(3-nitro-5-trifluoromethyl-phenoxy)-piperidine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-20 °C

Procedure

3-Nitro-5-trifluoromethyl-phenol (8.81 g) was dissolved in THF (76 ml). 1-Boc-4-hydroxy-piperidine (8.81 g, Aldrich) and Ph3P (11.15 g) were added and the solution was cooled to −20° C. A solution of DEAD (6.8 ml, Aldrich) in THF (36 ml) was added dropwise, maintaining the temperature between −20 and −10° C. The reaction was warmed to RT and stirred overnight. The reaction was concentrated in vacuo and triturated with hexane. The yellow solid was removed by filtration and washed with Et2O (25 ml), and hexane. The white filtrate was washed with 1N NaOH (2×), brine (1×) and the hexane layer was dried over Na2SO4, filtered and concentrated in vacuo. The crude material was purified with flash chromatography (SiO2, 5-10% EtOAc/hexane) to obtain 1-Boc-4-(3-nitro-5-trifluoromethyl-phenoxy)-piperidine.

Workup

  1. temperaturemaintaining the temperature between −20 and −10° C
  2. temperatureThe reaction was warmed to RT
  3. concentrationThe reaction was concentrated in vacuo
  4. customtriturated with hexane
  5. customThe yellow solid was removed by filtration
  6. washwashed with Et2O (25 ml), and hexane
  7. washThe white filtrate was washed with 1N NaOH (2×), brine (1×)
  8. dry with materialthe hexane layer was dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude material was purified with flash chromatography (SiO2, 5-10% EtOAc/hexane)

Sources & evidence

ORD record
ord-bbbbcfbd617546baa46da09e1cffacfa
Source dataset
uspto-grants-2009_04
Patent number
US07514564B2

Reaction notes

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