Acetic Acid → HCID 69151518, compound

HRID 1744087Notes

Reaction equation

HRID 1744087 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([C:20]3[C:24]([N:25](C(OCC(Cl)(Cl)Cl)=O)[C@H:26]([C:31]([O:33]C)=[O:32])[CH2:27][CH:28]([CH3:30])[CH3:29])=[CH:23][O:22][N:21]=3)=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(O)(=O)C>C1COCC1.[Zn]>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:15]=[CH:16][C:17]([C:20]3[C:24]([NH:25][C@H:26]([C:31]([OH:33])=[O:32])[CH2:27][CH:28]([CH3:29])[CH3:30])=[CH:23][O:22][N:21]=3)=[CH:18][CH:19]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:2])([CH3:4])[CH3:3]

Participants

5

Reactant 2

HCID 176Acetic AcidHCID 69152178HCID 69152178, compound

Product 1

HCID 69151518HCID 69151518, compoundYield 99.9%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl N-(3-{4-[4-(tert-butoxycarbonyl)piperazin-1-yl]phenyl}isoxazol-4-yl)-N-[(2,2,2-trichloroethoxy)carbonyl]leucinate (1.0 g, 1.55 mmol) in THF (20 mL) was added acetic acid (10 mL) and zinc dust (2.8 g, 42.8 mmol). The mixture was sonicated for 1 min, then stirred 1.5 h at room temperature. The solids were filtered through celite and the filtrate was co-evaporated with heptane. The residue was dissolved in ethyl acetate and washed with aqueous NaHCO3 and brine and concentrated. The residue was dissolved in methanol (25 mL) and 2 M LiOH (5 mL) was added. The mixture was stirred overnight at room temperature, then diluted with ethyl acetate and washed with pH 3 phosphate buffer. The organic phase was washed with brine and dried over MgSO4, and concentrated to give 710 mg of N-(3-{4-[4-(tert-butoxycarbonyl)piperazin-1-yl]phenyl}isoxazol-4-yl)leucine.

Workup

  1. customThe mixture was sonicated for 1 min
  2. filtrationThe solids were filtered through celite
  3. dissolutionThe residue was dissolved in ethyl acetate
  4. washwashed with aqueous NaHCO3 and brine
  5. concentrationconcentrated
  6. dissolutionThe residue was dissolved in methanol (25 mL)
  7. addition2 M LiOH (5 mL) was added
  8. stirringThe mixture was stirred overnight at room temperature
  9. additiondiluted with ethyl acetate
  10. washwashed with pH 3 phosphate buffer
  11. washThe organic phase was washed with brine
  12. dry with materialdried over MgSO4
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-3d440626b4f640958b505897cd578b88
Source dataset
uspto-grants-2006_03
Patent number
US07012075B2

Reaction notes

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