Triphenylphosphine → methyl N-(4-{4-[4-(tert-butoxycarbonyl)piperazin-1-yl]phenyl}-1,2,5-oxadiazol-3-yl)-N-[(2,2,2-trichloroethoxy)carbonyl]leucinate

HRID 1744124Notes

Reaction equation

HRID 1744124 reaction equation
[Cl:1][C:2]([Cl:33])([Cl:32])[CH2:3][O:4][C:5]([NH:7][C:8]1[C:9]([C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]3)=[CH:15][CH:14]=2)=[N:10][O:11][N:12]=1)=[O:6].O[CH:35]([CH2:40][CH:41]([CH3:43])[CH3:42])[C:36]([O:38][CH3:39])=[O:37].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>CN(C=O)C.O>[C:28]([O:27][C:25]([N:22]1[CH2:21][CH2:20][N:19]([C:16]2[CH:17]=[CH:18][C:13]([C:9]3[C:8]([N:7]([C:5]([O:4][CH2:3][C:2]([Cl:32])([Cl:1])[Cl:33])=[O:6])[C@H:35]([C:36]([O:38][CH3:39])=[O:37])[CH2:40][CH:41]([CH3:43])[CH3:42])=[N:12][O:11][N:10]=3)=[CH:14][CH:15]=2)[CH2:24][CH2:23]1)=[O:26])([CH3:30])([CH3:29])[CH3:31]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 62908Methyl 2-hydroxy-4-methylpentanoateHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 22235984Tert-butyl 4-[4-(4-{[(2,2,2-trichloroethoxy)carbonyl]amino}-1,2,5-oxadiazol-3-yl)phenyl]piperazine-1-carboxylate

Product 1

HCID 69152043methyl N-(4-{4-[4-(tert-butoxycarbonyl)piperazin-1-yl]phenyl}-1,2,5-oxadiazol-3-yl)-N-[(2,2,2-trichloroethoxy)carbonyl]leucinate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To tert-butyl 4-[4-(4-{[(2,2,2-trichloroethoxy)carbonyl]amino}-1,2,5-oxadiazol-3-yl)phenyl]piperazine-1-carboxylate (485 mg, 0.932 mmol), methyl 2-hydroxy-4-methylpentanoate (275 mg, 1.87 mmol) and triphenyl phosphine (490 mg, 1.87 mmol) in dry DMF (15 mL) at 0° C. under dry nitrogen was added diisopropyl azodicarboxylate (0.375 mL, 1.87 mmol) dropwise over ½ hour and the reaction mixture stirred overnight at rt. The reaction was poured into water and the product extracted with Et2O (2×), dried over Na2SO4, concentrated in vacuo and purified by flash chromatography over silica gel (EtOAc/Hex, 2/8) to afford methyl N-(4-{4-[4-(tert-butoxycarbonyl)piperazin-1-yl]phenyl}-1,2,5-oxadiazol-3-yl)-N-[(2,2,2-trichloroethoxy)carbonyl]leucinate.

Workup

  1. extractionthe product extracted with Et2O (2×)
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. custompurified by flash chromatography over silica gel (EtOAc/Hex, 2/8)

Sources & evidence

ORD record
ord-aaf776e94f924ed08ebb6056717309ce
Source dataset
uspto-grants-2006_03
Patent number
US07012075B2

Reaction notes

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