HCID 20610247, compound → HCID 20610318, compound

HRID 433817Notes

Reaction equation

HRID 433817 reaction equation
[CH2:1]([O:3][C:4](=[O:34])[C:5]([NH:27][C:28]([O:30][CH2:31][CH:32]=[CH2:33])=[O:29])([CH2:9][C:10]1[O:14][N:13]=[C:12]([CH:15]2[CH2:19][CH2:18][CH2:17][N:16]2[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH:11]=1)C(O)=O)[CH3:2].C(OC(=O)C(NC(OCC=C)=O)(CC1ON=C(C2CCCN2C(OC(C)(C)C)=O)C=1)C(OCC)=O)C>O1CCOCC1>[C:23]([O:22][C:20]([N:16]1[CH2:17][CH2:18][CH2:19][CH:15]1[C:12]1[CH:11]=[C:10]([CH2:9][CH:5]([NH:27][C:28]([O:30][CH2:31][CH:32]=[CH2:33])=[O:29])[C:4]([O:3][CH2:1][CH3:2])=[O:34])[O:14][N:13]=1)=[O:21])([CH3:26])([CH3:25])[CH3:24]

Participants

4

Reactant 2

HCID 20610247HCID 20610247, compoundHCID 20610270HCID 20610270, compound

Product 1

HCID 20610318HCID 20610318, compoundYield 56%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
125 °C

Procedure

A mixture of 2-allyloxycarbonylamino-2-[3-(1-tert-butoxycarbonyl-pyrrolidin-2-yl)-isoxazol-5-ylmethyl]-malonic acid monoethyl ester and 2-allyloxycarbonylamino-2-[3-(1-tert-butoxycarbonyl-pyrrolidin-2-yl)-isoxazol-5-ylmethyl]-malonic acid diethyl ester (10.4 g, 21.5 mmol) was dissolved in dioxane (130 mL) and heated in an oil bath to 125° C. for 3 hours. The dioxane was then removed in vacuo. The residue was dissolved in ethyl acetate, washed with saturated sodium carbonate and brine, dried over magnesium sulfate and concentrated. The crude material was chromatographed on a Biotage Flash 40M column eluting with ethyl acetate/hexanes (1:4) to give the title compound as a clear oil (5.12 g, 56% 2 steps). MS (CI) m/z 338.0 (M-99). 2-Allyloxycarbonylamino-2-[3-(1-tert-butoxycarbonyl-pyrrolidin-2-yl)-isoxazol-5-ylmethyl]-malonic acid diethyl ester was recovered (2.96 g, 27%). MS (CI) m/z 509.9 (M+1), 409.9 (M−99)

Workup

  1. customThe dioxane was then removed in vacuo
  2. dissolutionThe residue was dissolved in ethyl acetate
  3. washwashed with saturated sodium carbonate and brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. customThe crude material was chromatographed on a Biotage Flash 40M column
  7. washeluting with ethyl acetate/hexanes (1:4)

Sources & evidence

ORD record
ord-5c76c4a7daf5438cab96058325b857ae
Source dataset
uspto-grants-2003_12
Patent number
US06668527B2

Reaction notes

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