Triethylamine → cis-1-Acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinamine

HRID 2366858Notes

Reaction equation

HRID 2366858 reaction equation
[Cl-].[Al+3].[Cl-].[Cl-].CC(OC(=O)[NH:10][C@H:11]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([Br:21])[CH:19]=2)[N:14]([C:22](=[O:24])[CH3:23])[C@@H:13]([CH3:25])[CH2:12]1)C.C(N(CC)CC)C.CCOC(C)=O>ClCCl.CO>[C:22]([N:14]1[C:15]2[C:20](=[CH:19][C:18]([Br:21])=[CH:17][CH:16]=2)[C@H:11]([NH2:10])[CH2:12][C@@H:13]1[CH3:25])(=[O:24])[CH3:23]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 6451240Aluminum(III) ChlorideHCID 529350201-Methylethyl((cis)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate

Product 1

HCID 67194540cis-1-Acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinamine

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a suspension of aluminium chloride (6.97 g, 52.3 mmol) in dichloromethane (DCM) (80 mL) at 0° C. under nitrogen was added 1-methylethyl[(2S,4R)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (for a preparation, see Example 4) (5.08 g, 13.76 mmol) in DCM (10 mL). The resulting mixture was stirred for 30 min then triethylamine (23.01 mL, 165 mmol) in methanol (8 mL) was slowly added to the mixture. AcOEt (200 mL) was added and the resulting mixture was stirred at room temperature for 15 min. The precipitate formed was filtered off and rinsed with AcOEt then partitioned between a saturated NaHCO3 aqueous solution and DCM (200 mL each). The biphasic mixture was vigorously stirred for 2 h. The two layers were separated and the organic phase was dried using a phase separator then concentrated in vacuo to give a first batch of (2S,4R)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinamine. The aqueous layer was treated with another 200 mL of DCM and the resulting biphasic mixture was vigorously stirred for 20 min. The two layers were separated and the organic phase was dried using a phase separator then concentrated in vacuo to give a second batch of (2S,4R)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinamine. Both batches were combined to give (2S,4R)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinamine (3.65 g, 12.7 mmol, 93%) as white solid which was used in the next step without further purification.

Workup

  1. customfor a preparation
  2. stirringthe resulting mixture was stirred at room temperature for 15 min
  3. customThe precipitate formed
  4. filtrationwas filtered off
  5. washrinsed with AcOEt
  6. customthen partitioned between a saturated NaHCO3 aqueous solution and DCM (200 mL each)
  7. stirringThe biphasic mixture was vigorously stirred for 2 h
  8. customThe two layers were separated
  9. customthe organic phase was dried
  10. concentrationthen concentrated in vacuo

Sources & evidence

ORD record
ord-ff9f06537d62458d9aaf389bae9e766a
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Reaction notes

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