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

HRID 572333Notes

Reaction equation

HRID 572333 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 85.4%

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 isopropyl ((2S,4R)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)carbamate (30 g, 81 mmol) in DCM (80 ml) via cannula and the resulting mixture was stirred at this temperature for 30 minutes. 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 NaHCO3 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, 2 min), 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 NaHCO3 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-ba596a69b9f0478cb56f3143dd21a6e3
Source dataset
uspto-grants-2015_05
Patent number
US09029395B2

Reaction notes

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