Acetic Acid → HCID 68185441, compound

HRID 2366973Notes

Reaction equation

HRID 2366973 reaction equation
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([N:14]([C:19](=O)[CH3:20])[CH2:15][C:16](=O)[CH3:17])=[CH:11][CH:12]=2)[C@H:7]([NH:22][C:23](=[O:28])[O:24][CH:25]([CH3:27])[CH3:26])[CH2:6][C@@H:5]1[CH3:29])(=[O:3])[CH3:2].C([O-])(=O)C.[NH4+:34].C(O)(=O)C.[OH-].[Na+]>C(Cl)Cl.CO.CCOC(C)=O>[CH3:27][CH:25]([O:24][C:23](=[O:28])[NH:22][C@H:7]1[C:8]2[C:13](=[CH:12][CH:11]=[C:10]([N:14]3[CH:15]=[C:16]([CH3:17])[N:34]=[C:19]3[CH3:20])[CH:9]=2)[N:4]([C:1](=[O:3])[CH3:2])[C@@H:5]([CH3:29])[CH2:6]1)[CH3:26]

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 517165Ammonium AcetateHCID 68185408HCID 68185408, compound

Product 1

HCID 68185441HCID 68185441, compoundYield 19%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 1-methylethyl {(2S,4R)-1-acetyl-6-[acetyl(2-oxopropyl)amino]-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl}carbamate (for a preparation see Intermediate 110) (130 mg, 0.322 mmol), ammonium acetate (124 mg, 1.611 mmol) and acetic acid (2 mL, 34.9 mmol) was stirred at 120° C. under nitrogen for 24 h then cooled to room temperature and basified with NaOH (2N in water). The mixture was then partitioned between AcOEt (10 mL) and water (5 mL) and the phases were separated. The organic layer was washed with a saturated NaHCO3 aqueous solution, dried over Na2SO4 and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (gradient: 100% AcOEt then 0 to 10% MeOH in DCM) gave 1-methylethyl[(2S,4R)-1-acetyl-6-(2,4-dimethyl-1H-imidazol-1-yl)-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (28 mg, 0.062 mmol, 19%) as a yellow gum.

Workup

  1. temperaturethen cooled to room temperature
  2. customThe mixture was then partitioned between AcOEt (10 mL) and water (5 mL)
  3. customthe phases were separated
  4. washThe organic layer was washed with a saturated NaHCO3 aqueous solution
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customPurification of the residue by flash chromatography on silica gel (gradient

Sources & evidence

ORD record
ord-78581d16d53748afb7030100e34beff4
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Reaction notes

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