Hydrochloric Acid → HCID 59003235, compound

HRID 2353944Notes

Reaction equation

HRID 2353944 reaction equation
COC(=O)[C:4]1[C:9]([CH3:10])=[CH:8][CH:7]=[CH:6][C:5]=1[N:11]([CH2:18][CH2:19][CH2:20][C:21]([O:23]CC)=O)[C:12]([O:14][CH:15]([CH3:17])[CH3:16])=[O:13].CC(C)([O-])C.[K+].Cl.[Cl-].[Li+]>C1COCC1.[Cl-].[Na+].O>[CH:15]([O:14][C:12]([N:11]1[CH2:18][CH2:19][CH2:20][C:21](=[O:23])[C:4]2[C:9]([CH3:10])=[CH:8][CH:7]=[CH:6][C:5]1=2)=[O:13])([CH3:16])[CH3:17]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 433294Lithium ChlorideHCID 23665647Potassium tert-butoxideHCID 59003218HCID 59003218, compound

Product 1

HCID 59003235HCID 59003235, compoundYield 27.4%

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]-6-methyl-benzoic acid methyl ester (4.60 g, 12.6 mmol) in THF (197 mL) to a solution of potassium tert-butoxide (25.2 mL, 25.2 mmol, 1 M in THF) in THF (175 mL) at room temperature under an atmosphere of nitrogen. After 30 min, 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 sodium sulfate, filter, and remove the solvent under reduced pressure. Dissolve the former crude in DMSO (101 mL) and add water (8 drops) followed by addition of lithium chloride (1.32 g, 31.5 mmol) and heat the resulting solution at 160° C. for 45 minutes. Cool the mixture to room temperature and pour into brine. Extract the mixture with ethyl acetate. Dry the organic layers over anhydrous sodium 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 (903 mg, 27% over two steps): MS (ES+): 262 (M+H).

Workup

  1. extractionextract with dichloromethane
  2. dry with materialDry the organic layer over anhydrous sodium sulfate
  3. filtrationfilter
  4. customremove the solvent under reduced pressure
  5. dissolutionDissolve the former crude in DMSO (101 mL)
  6. additionadd water (8 drops)
  7. temperatureCool the mixture to room temperature
  8. extractionExtract the mixture with ethyl acetate
  9. dry with materialDry the organic layers over anhydrous sodium 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-436455c1e79b4e829e86483a5452d0d6
Source dataset
uspto-grants-2010_07
Patent number
US07749992B2

Reaction notes

Loading…