Ethyl Acetate → HCID 66894693, compound

HRID 19393Notes

Reaction equation

HRID 19393 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:11])[C@H:5]([CH2:7][CH:8]([CH3:10])[CH3:9])[NH2:6].C([O:14][C:15](=O)/[CH:16]=[C:17](/[O:20][C:21]1[C:26]2[N:27]=[C:28]([CH3:30])[O:29][C:25]=2[CH:24]=[CH:23][CH:22]=1)\[CH2:18]Br)C.C(N(CC)C(C)C)(C)C.C(OCC)(=O)C>C(#N)C>[CH3:2][O:3][C:4](=[O:11])[C@@H:5]([N:6]1[CH2:18][C:17]([O:20][C:21]2[C:26]3[N:27]=[C:28]([CH3:30])[O:29][C:25]=3[CH:24]=[CH:23][CH:22]=2)=[CH:16][C:15]1=[O:14])[CH2:7][CH:8]([CH3:10])[CH3:9]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 2723695Leucine methyl ester hydrochlorideHCID 66894865(E)-4-bromo-3-(2-methyl-benzooxazol-4-yloxy)-but-2-enoic acid ethyl ester

Product 1

HCID 66894693HCID 66894693, compoundYield 56%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (L)-leucine methyl ester hydrochloride (0.570 g, 3.14 mmol), (E)-4-bromo-3-(2-methyl-benzooxazol-4-yloxy)-but-2-enoic acid ethyl ester (0.970 g, 2.85 mmol) and N,N-diisopropylethylamine (0.809 g, 6.21 mmol) in acetonitrile (20 mL) in a sealed tube was heated at 100° C. for 5 h. The reaction mixture was then cooled to room temperature and ethyl acetate was added. The mixture was then filtered. The filtrate was washed successively with aqueous saturated ammonium chloride, water, and brine and then dried over sodium sulfate, filtered and concentrated in vacuo. The residue was dissolved in tetrahydrofuran (5 mL) and microwaved in an Emry Optimizer microwave reaction vessel at 160° C., for 3 h. The mixture was then cooled and concentrated in vacuo and the residue was purified by ISCO Combiflash chromatography (40 g Silicycle, 5% to 50% ethyl acetate/hexanes) to afford (S)-4-methyl-2-[4-(2-methyl-benzooxazol-4-yloxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-pentanoic acid methyl ester (0.570 g, 56%) as a brown oil.

Workup

  1. temperatureThe reaction mixture was then cooled to room temperature
  2. filtrationThe mixture was then filtered
  3. washThe filtrate was washed successively with aqueous saturated ammonium chloride, water, and brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residue was dissolved in tetrahydrofuran (5 mL)
  8. custommicrowaved in an Emry Optimizer microwave reaction vessel at 160° C., for 3 h
  9. temperatureThe mixture was then cooled
  10. concentrationconcentrated in vacuo
  11. customthe residue was purified by ISCO Combiflash chromatography (40 g Silicycle, 5% to 50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-c340630b5e7a4d41953dd76d267699a5
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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