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

HRID 1744138Notes

Reaction equation

HRID 1744138 reaction equation
[CH3:1][C:2]1[C:6]([C:7]2[CH:12]=[CH:11][C:10]([N:13]3[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]3)=[CH:9][CH:8]=2)=[C:5]([NH:26][C:27]([O:29][CH2:30][C:31]([Cl:34])([Cl:33])[Cl:32])=[O:28])[O:4][N:3]=1.O[CH:36]([CH2:41][CH:42]([CH3:44])[CH3:43])[C:37]([O:39][CH3:40])=[O:38].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:22]([O:21][C:19]([N:16]1[CH2:15][CH2:14][N:13]([C:10]2[CH:9]=[CH:8][C:7]([C:6]3[C:2]([CH3:1])=[N:3][O:4][C:5]=3[N:26]([C:27]([O:29][CH2:30][C:31]([Cl:32])([Cl:33])[Cl:34])=[O:28])[C@H:36]([C:37]([O:39][CH3:40])=[O:38])[CH2:41][CH:42]([CH3:44])[CH3:43])=[CH:12][CH:11]=2)[CH2:18][CH2:17]1)=[O:20])([CH3:25])([CH3:23])[CH3:24]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 62908Methyl 2-hydroxy-4-methylpentanoateHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 22235871Tert-butyl 4-[4-(3-methyl-5-{[(2,2,2-trichloroethoxy)carbonyl]amino}isoxazol-4-yl)phenyl]piperazine-1-carboxylate

Product 1

HCID 69151299methyl N-(4-{4-[4-(tert-butoxycarbonyl)piperazin-1-yl]phenyl}-3-methylisoxazol-5-yl)-N-[(2,2,2-trichloroethoxy)carbonyl]leucinate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To tert-butyl 4-[4-(3-methyl-5-{[(2,2,2-trichloroethoxy)carbonyl]amino}isoxazol-4-yl)phenyl]piperazine-1-carboxylate (617 mg, 1.16 mmol), methyl 2-hydroxy-4-methylpentanoate (255 mg, 1.74 mmol) and triphenyl phosphine (460 mg, 1.74 mmol) in dry DMF (15 mL) at 0° C. under dry nitrogen was added diisopropyl azodicarboxylate (0.35 mL, 1.74 mmol) dropwise over ½ hour and the reaction mixture was stirred for 2 days 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, 25/75) to afford methyl N-(4-{4-[4-(tert-butoxycarbonyl)piperazin-1-yl]phenyl}-3-methylisoxazol-5-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, 25/75)

Sources & evidence

ORD record
ord-07c8842a9e734c719b657c830ca25409
Source dataset
uspto-grants-2006_03
Patent number
US07012075B2

Reaction notes

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