Triethylamine → HCID 67195867, compound

HRID 2041708Notes

Reaction equation

HRID 2041708 reaction equation
[Cl-].[Al+3].[Cl-].[Cl-].[C:5]([N:8]1[C:17]2[C:12](=[CH:13][C:14]([C:18]3[CH:23]=[CH:22][C:21]([CH2:24][N:25]4[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]4)=[CH:20][CH:19]=3)=[CH:15][CH:16]=2)[C@H:11]([NH:31]C(=O)OC(C)C)[CH2:10][C@@H:9]1[CH3:38])(=[O:7])[CH3:6].C(N(CC)CC)C.CCOC(C)=O>C(Cl)Cl.CO>[C:5]([N:8]1[C:17]2[C:12](=[CH:13][C:14]([C:18]3[CH:23]=[CH:22][C:21]([CH2:24][N:25]4[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]4)=[CH:20][CH:19]=3)=[CH:15][CH:16]=2)[C@H:11]([NH2:31])[CH2:10][C@@H:9]1[CH3:38])(=[O:7])[CH3:6]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 6451240Aluminum(III) ChlorideHCID 52935018HCID 52935018, compound

Product 1

HCID 67195867HCID 67195867, compoundYield 18.12%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

A suspension of aluminium chloride (1.053 g, 7.89 mmol) in DCM (10 mL) at room temperature under nitrogen was treated with 1-methylethyl {(2S,4R)-1-acetyl-2-methyl-6-[4-(1-piperidinylmethyl)phenyl]-1,2,3,4-tetrahydro-4-quinolinyl}carbamate (for a preparation see intermediate 67) (0.915 g, 1.974 mmol) as a solution in DCM (2.5 mL) and the resulting mixture was stirred at room temperature for 1 h then cooled using an ice bath and treated with triethylamine (3.30 ml, 23.68 mmol) in methanol (2 mL) producing a thick precipitate. AcOEt (25 mL) was added to the thick precipitate formed and the mixture was stirred for 30 min. The precipitate was filtered off and partitioned between a saturated NaHCO3 aqueous solution (50 mL) and AcOEt (50 mL). The resulting biphasic mixture was stirred at room temperature for 30 min and then the layers were separated. The aqueous layer was stirred with 1:1 DCM:AcOEt (50 mL) and the organic layer was collected using a hydrophobic frit. This was repeated twice. The first AcOEt phase was also eluted through the hydrophobic frit and the combined organics concentrated in vacuovacuo. Purification of the residue by flash chromatography on silica gel using a 100 G silica cartridge (gradient:1 to 10% (2N NH3 in MeOH) in DCM) gave (2S,4R)-1-acetyl-2-methyl-6-[4-(1-piperidinylmethyl)phenyl]-1,2,3,4-tetrahydro-4-quinolinamine (150 mg, 0.358 mmol, 18.12% yield) as a yellow oil.

Workup

  1. temperaturethen cooled
  2. customproducing a thick precipitate
  3. customformed
  4. stirringthe mixture was stirred for 30 min
  5. filtrationThe precipitate was filtered off
  6. custompartitioned between a saturated NaHCO3 aqueous solution (50 mL) and AcOEt (50 mL)
  7. stirringThe resulting biphasic mixture was stirred at room temperature for 30 min
  8. customthe layers were separated
  9. stirringThe aqueous layer was stirred with 1:1 DCM
  10. customAcOEt (50 mL) and the organic layer was collected
  11. washThe first AcOEt phase was also eluted through the hydrophobic frit
  12. concentrationthe combined organics concentrated in vacuovacuo
  13. customPurification of the residue by flash chromatography on silica gel using a 100 G silica cartridge (gradient:1 to 10% (2N NH3 in MeOH) in DCM)

Sources & evidence

ORD record
ord-29ee68fd9699463ba67534f77a9e9f8e
Source dataset
uspto-grants-2013_11
Patent number
US08580957B2

Reaction notes

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