Water → HCID 89560334, compound

HRID 1747223Notes

Reaction equation

HRID 1747223 reaction equation
C([O:3][C:4](=[O:28])[C:5]([NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])([CH2:11][C:12]1[CH:17]=[C:16]([I:18])[CH:15]=[CH:14][C:13]=1[F:19])C(OCC)=O)C.O.[OH-].[Na+]>CCO>[C:24]([O:23][C:21]([NH:20][CH:5]([CH2:11][C:12]1[CH:17]=[C:16]([I:18])[CH:15]=[CH:14][C:13]=1[F:19])[C:4]([OH:28])=[O:3])=[O:22])([CH3:27])([CH3:25])[CH3:26]

Participants

5

Reactant 3

HCID 962WaterHCID 14798Sodium HydroxideHCID 89560050HCID 89560050, compound

Product 1

HCID 89560334HCID 89560334, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
40 °C

Procedure

A suspension of 2-tert-butoxycarbonylamino-2-(2-fluoro-5-iodo-benzyl)-malonic acid diethyl ester G-22 in EtOH (113 mL) was heated to 40° C. and water (50 mL) was then added giving an easily stirrable emulsion. 1M aq. NaOH (93 mL) was carefully added and reaction mixture was heated to 100° C. for 16 h. The reaction mixture was cooled to RT and the volatiles were removed in vacuo. The remaining aqueous phase was extracted once with TBME and this extract was discarded. The aqueous layer was acidified with 25% aq. HCl and extracted with TBME (2×). The combined organic layers were washed with water, dried over Na2SO4, filtered and evaporated in vacuo to give the crude product that was purified by flash chromatography (eluting with a gradient of 25% to 50% EtOAc in hexane) to give the title compound as a white solid. LC-MS B: tR=0.80 min; [M-Me]+=394.95.

Workup

  1. customgiving an easily stirrable emulsion
  2. customreaction mixture
  3. temperaturewas heated to 100° C. for 16 h
  4. temperatureThe reaction mixture was cooled to RT
  5. customthe volatiles were removed in vacuo
  6. extractionThe remaining aqueous phase was extracted once with TBME
  7. extractionextracted with TBME (2×)
  8. washThe combined organic layers were washed with water
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. customevaporated in vacuo
  12. customto give the crude product that
  13. customwas purified by flash chromatography (
  14. washeluting with a gradient of 25% to 50% EtOAc in hexane)

Sources & evidence

ORD record
ord-ddc46c5a9ef14a14a389420a696c20db
Source dataset
uspto-grants-2015_10
Patent number
US09150566B2

Reaction notes

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