Triphenylphosphine → Tert-butyl 4-[6-(4-cyclohexyl-3-trifluoromethyl-phenoxymethyl)-pyridin-3-yl]-piperazine-1-carboxylate

HRID 2100667Notes

Reaction equation

HRID 2100667 reaction equation
[OH:1][CH2:2][C:3]1[N:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)=[CH:5][CH:4]=1.[CH:22]1([C:28]2[CH:33]=[CH:32][C:31](O)=[CH:30][C:29]=2[C:35]([F:38])([F:37])[F:36])[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C(Cl)Cl>[CH:22]1([C:28]2[CH:33]=[CH:32][C:31]([O:1][CH2:2][C:3]3[N:8]=[CH:7][C:6]([N:9]4[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]4)=[CH:5][CH:4]=3)=[CH:30][C:29]=2[C:35]([F:36])([F:37])[F:38])[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 68814347Tert-butyl 4-(6-hydroxymethyl-pyridin-3-yl)-piperazine-1-carboxylateHCID 688157504-Cyclohexyl-3-trifluoromethyl-phenol

Product 1

HCID 68815760Tert-butyl 4-[6-(4-cyclohexyl-3-trifluoromethyl-phenoxymethyl)-pyridin-3-yl]-piperazine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-Butyl 4-(6-hydroxymethyl-pyridin-3-yl)-piperazine-1-carboxylate (0.22 mmol), 4-Cyclohexyl-3-trifluoromethyl-phenol (0.22 mmol, synthesized in a similar manner as described in a previous example), 1,1′-azodicarbonyl dipiperdine (0.33 mmol) and Ph3P (0.33 mmol) are mixed in DCM (2 mL). The reaction mixture is stirred at room temperature for 17 h and then partitioned between saturated Na2CO3 solution and EtOAc. The aqueous phase is extracted with EtOAc. The combined organic extracts are washed with saturated aqueous NaCl and dried over Na2SO4. After concentration, the residue is purified by silica gel chromatography (6:5 hexanes/EtOAc) to give tert-butyl 4-[6-(4-cyclohexyl-3-trifluoromethyl-phenoxymethyl)-pyridin-3-yl]-piperazine-1-carboxylate.

Workup

  1. custompartitioned between saturated Na2CO3 solution and EtOAc
  2. extractionThe aqueous phase is extracted with EtOAc
  3. washThe combined organic extracts are washed with saturated aqueous NaCl
  4. dry with materialdried over Na2SO4
  5. concentrationAfter concentration
  6. customthe residue is purified by silica gel chromatography (6:5 hexanes/EtOAc)

Sources & evidence

ORD record
ord-5849b5898ccd4753a10c02e18f5d15c5
Source dataset
uspto-grants-2009_08
Patent number
US07572811B2

Reaction notes

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