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

HRID 628949Notes

Reaction equation

HRID 628949 reaction equation
[Cl-].[Al+3].[Cl-].[Cl-].[C:5]([N:8]1[C:17]2[C:12](=[CH:13][C:14]([Br:18])=[CH:15][CH:16]=2)[C@H:11]([NH:19]C(=O)OC(C)C)[CH2:10][C@@H:9]1[CH3:26])(=[O:7])[CH3:6].C(N(CC)CC)C.CO>C(Cl)Cl.C(OCC)(=O)C>[NH2:19][C@H:11]1[C:12]2[C:17](=[CH:16][CH:15]=[C:14]([Br:18])[CH:13]=2)[N:8]([C:5](=[O:7])[CH3:6])[C@@H:9]([CH3:26])[CH2:10]1

Participants

7

Reactant 4

HCID 887MethanolHCID 8471TriethylamineHCID 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-quinolinamineYield 85%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A suspension of aluminium chloride (41.2 g, 309 mmol) in DCM (480 ml) at 0° C. under nitrogen was treated with a solution of 1-methylethyl ((2S,4R)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)carbamate (for a preparation see Intermediate 1) (30 g, 81 mmol) in DCM (80 ml) via cannula and the resulting mixture was stirred at this temperature for 30 min. The reaction mixture was then slowly treated with a mixture of triethylamine (136 ml, 975 mmol) and methanol (48 ml) via cannula. The resulting cake formed was stirred in ethyl acetate (800 ml), isolated by filtration and subsequently partitioned between DCM (800 ml) and saturated aqueous sodium hydrogen carbonate solution (800 ml). Sodium potassium tartrate (300 g) was added and the resulting mixture was stirred vigorously for 2 h. The layers were separated and the DCM layer was filtered through a sinter funnel. The filtrate was dried (MgSO4) and concentrated in vacuo to give a first crop of 1-((2S,4R)-4-amino-6-bromo-2-methyl-3,4-dihydroquinolin-1(2H)-yl)ethanone (19.6 g, 69.2 mmol, 85% yield) as a yellow foam. The aqueous phase was treated further with DCM (800 ml) and the biphasic mixture stirred overnight. The layers were then separated and the organic layer was dried over (MgSO4) and concentrated in vacuo to give a second crop of 1-((2S,4R)-4-amino-6-bromo-2-methyl-3,4-dihydroquinolin-1(2H)-yl)ethanone (3.4 g, 12.01 mmol, 14.78% yield). LCMS (HpH), Rt 0.77 min, MH+ 283 (1 Br).

Workup

  1. customThe resulting cake formed
  2. customisolated by filtration
  3. customsubsequently partitioned between DCM (800 ml) and saturated aqueous sodium hydrogen carbonate solution (800 ml)
  4. additionSodium potassium tartrate (300 g) was added
  5. stirringthe resulting mixture was stirred vigorously for 2 h
  6. customThe layers were separated
  7. filtrationthe DCM layer was filtered through a sinter funnel
  8. dry with materialThe filtrate was dried (MgSO4)
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-28c0b26ed2d54ddc98a3fc37ab3329d3
Source dataset
uspto-grants-2016_04
Patent number
US09315487B2

Reaction notes

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