Dichloromethane → ethyl 4-((2S,4R)-1-acetyl-4-amino-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)benzoate

HRID 572346Notes

Reaction equation

HRID 572346 reaction equation
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:24]=[CH:23][C:17]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:16][CH:15]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:25]C(OC(C)C)=O)[CH2:6][C@@H:5]1[CH3:32])(=[O:3])[CH3:2].[Cl-].[Al+3].[Cl-].[Cl-].C(N(CC)CC)C.C(Cl)Cl>CO>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:24]=[CH:23][C:17]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:16][CH:15]=3)=[CH:11][CH:12]=2)[C@H:7]([NH2:25])[CH2:6][C@@H:5]1[CH3:32])(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 6451240Aluminum(III) ChlorideHCID 67206518Ethyl 4-[(2S,4R)-1-acetyl-2-methyl-4-({[(1-methylethyl)oxy]carbonyl}amino)-1,2,3,4-tetrahydro-6-quinolinyl]benzoate

Product 1

HCID 67205707ethyl 4-((2S,4R)-1-acetyl-4-amino-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)benzoate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The same reaction was done in parallel, using of ethyl 4-[(2S,4R)-1-acetyl-2-methyl-4-({[(1-methylethyl)oxy]carbonyl}amino)-1,2,3,4-tetrahydro-6-quinolinyl]benzoate (for a preparation see Intermediate 15) (0.89 g 2.030 mmol), aluminium chloride (1.03 g, 7.72 mmol), triethylamine (3.4 mL, 24.53 mmol), DCM (16 mL) and MeOH (1.3 mL). The products of both reactions were combined at this stage and the resulting mixture was stirred at room temperature for approximately 10 min (total volume: approximately 1 L). The mixture was filtered through Celite™, the insoluble residue was washed with EtOAc and a saturated NaHCO3 aqueous solution and the layers were separated. The aqueous phase was extracted with EtOAc and the combined organic phases were washed with brine, dried (hydrophobic frit) and concentrated in vacuo to give ethyl 4-[(2S,4R)-1-acetyl-4-amino-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl]benzoate (6.6 g, 84%—allowing for the addition of the parallel experiment) as a cream solid. LCMS (formate, 2 min), Retention time 0.73 min, [M-NH2]+=336

Workup

  1. customThe same reaction
  2. filtrationThe mixture was filtered through Celite™
  3. washthe insoluble residue was washed with EtOAc
  4. customa saturated NaHCO3 aqueous solution and the layers were separated
  5. extractionThe aqueous phase was extracted with EtOAc
  6. washthe combined organic phases were washed with brine
  7. customdried (hydrophobic frit)
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-375d3ff1c7114e6ca47d5a72a16d4016
Source dataset
uspto-grants-2015_05
Patent number
US09029395B2

Reaction notes

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