Hydrochloric Acid → HCID 59432457, compound

HRID 2353948Notes

Reaction equation

HRID 2353948 reaction equation
COC(=O)[C:4]1[CH:9]=[CH:8][C:7]([Br:10])=[C:6]([CH3:11])[C:5]=1[N:12]([CH2:19][CH2:20][CH2:21][C:22]([O:24]CC)=O)[C:13]([O:15][CH:16]([CH3:18])[CH3:17])=[O:14].CC(C)([O-])C.[K+].Cl.[Cl-].[Li+]>C1COCC1.[Cl-].[Na+].O>[CH:16]([O:15][C:13]([N:12]1[CH2:19][CH2:20][CH2:21][C:22](=[O:24])[C:4]2[CH:9]=[CH:8][C:7]([Br:10])=[C:6]([CH3:11])[C:5]1=2)=[O:14])([CH3:17])[CH3:18]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 433294Lithium ChlorideHCID 23665647Potassium tert-butoxideHCID 68681230HCID 68681230, compound

Product 1

HCID 59432457HCID 59432457, compoundYield 75.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
160 °C

Procedure

Add a solution of 2-[(3-Ethoxycarbonyl-propyl)-isopropoxycarbonyl-amino]-4-bromo-3-methyl-benzoic acid methyl ester (3.47 g, 7.81 mmol) in THF (120 mL) to a solution of potassium tert-butoxide (15.6 mL, 15.62 mmol, 1 M in THF) in THF (120 mL) at room temperature under an atmosphere of nitrogen. After 2 h, pour the mixture into ice/water. Treat aqueous phase with 1M HCl to pH neutral and extract with dichloromethane. Dry the organic layer over anhydrous magnesium sulfate, filter, and remove the solvent under reduced pressure. Dissolve the former crude in DMSO (66 mL) and add water (4 drops) followed by addition of lithium chloride (0.882 g, 20.8 mmol) and heat the resulting solution at 160° C. for 2 h. Cool the mixture to room temperature and pour into brine. Extract the mixture with ethyl acetate. Dry the organic layers over anhydrous magnesium sulfate, filter and remove the solvent under reduced pressure. Purify the residue by flash chromatography, eluting with hexanes/ethyl acetate, to afford the title compound (2.0 g, 72% over two steps): MS (ES+): 341 (M+H).

Workup

  1. extractionextract with dichloromethane
  2. dry with materialDry the organic layer over anhydrous magnesium sulfate
  3. filtrationfilter
  4. customremove the solvent under reduced pressure
  5. dissolutionDissolve the former crude in DMSO (66 mL)
  6. additionadd water (4 drops)
  7. temperatureCool the mixture to room temperature
  8. extractionExtract the mixture with ethyl acetate
  9. dry with materialDry the organic layers over anhydrous magnesium sulfate
  10. filtrationfilter
  11. customremove the solvent under reduced pressure
  12. customPurify the residue by flash chromatography
  13. washeluting with hexanes/ethyl acetate

Sources & evidence

ORD record
ord-2023753102d1406da7e058c2b614f6ce
Source dataset
uspto-grants-2010_07
Patent number
US07749992B2

Reaction notes

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