Aniline → 8-bromo-N-phenylquinolin-2-amine

HRID 1055979Notes

Reaction equation

HRID 1055979 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Br:8][C:9]1[CH:10]=[CH:11][CH:12]=[C:13]2[C:18]=1[N:17]=[C:16](Cl)[CH:15]=[CH:14]2.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[Br:8][C:9]1[CH:10]=[CH:11][CH:12]=[C:13]2[C:18]=1[N:17]=[C:16]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[CH:15]=[CH:14]2

Participants

5

Reactant 3

HCID 6115AnilineHCID 2733832Lithium HexamethyldisilazideHCID 109557558-Bromo-2-chloroquinoline

Product 1

HCID 897821908-bromo-N-phenylquinolin-2-amineYield 76%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of aniline (0.76 g, 8.16 mmol) and 8-bromo-2-chloroquinoline (Biofine International, Vancouver, BC; 1.1 g, 4.54 mmol) in THF (7 mL) at 0° C. was added LiHMDS (1.0 M solution in THF, 13.61 mL, 13.61 mmol) drop wise via a syringe. The resulting brown mixture was stirred at RT for 1 h, and then quenched with sat. NH4Cl solution (15 mL) and extracted with EtOAc (2×50 mL). The combined organic solution was concentrated and the residue was purified on a silica gel column (25-45% EtOAc in hexanes) to afford 8-bromo-N-phenylquinolin-2-amine (Ex. 165c, 1.03 g, 3.44 mmol, 76% yield) as a brown crystalline solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.69 (1H, s), 8.21 (2H, d, J=7.8 Hz), 8.10 (1H, d, J=8.8 Hz), 7.94 (1H, m), 7.77 (1H, d, J=7.0 Hz), 7.35 (2H, t, J=7.8 Hz), 7.21 (1H, t, J=7.7 Hz), 7.13 (1H, d, J=9.0 Hz), 6.98 (1H, t, J=7.3 Hz). m/z (ESI, +ve) 299/301 (M+H)+.

Workup

  1. customquenched with sat. NH4Cl solution (15 mL)
  2. extractionextracted with EtOAc (2×50 mL)
  3. concentrationThe combined organic solution was concentrated
  4. customthe residue was purified on a silica gel column (25-45% EtOAc in hexanes)

Sources & evidence

ORD record
ord-7e1c5553458f4052811a2387340e3d17
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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