1-(5-Bromo-3,4-dihydroquinolin-1(2H)-yl)-4-(2,3-dimethylphenoxy)butan-1-one → 1-(4-(2,3-Dimethylphenoxy)butanoyl)-1,2,3,4-tetrahydroquinoline-5-carbonitrile

HRID 2175264Notes

Reaction equation

HRID 2175264 reaction equation
Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][CH2:6][N:7]2[C:12](=[O:25])[CH2:13][CH2:14][CH2:15][O:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([CH3:23])[C:18]=1[CH3:24].[C:26]([Zn]C#N)#[N:27]>CN(C=O)C.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:24][C:18]1[C:19]([CH3:23])=[CH:20][CH:21]=[CH:22][C:17]=1[O:16][CH2:15][CH2:14][CH2:13][C:12]([N:7]1[C:8]2[CH:9]=[CH:10][CH:11]=[C:2]([C:26]#[N:27])[C:3]=2[CH2:4][CH2:5][CH2:6]1)=[O:25]

Participants

6

Reactant 2

HCID 709817961-(5-Bromo-3,4-dihydroquinolin-1(2H)-yl)-4-(2,3-dimethylphenoxy)butan-1-oneHCID 178514179HCID 178514179, compound

Product 1

HCID 709826251-(4-(2,3-Dimethylphenoxy)butanoyl)-1,2,3,4-tetrahydroquinoline-5-carbonitrileYield 86.1%

Reagents, catalysts & solvents 3

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

To a degassed solution of 1-(5-bromo-3,4-dihydroquinolin-1(2H)-yl)-4-(2,3-dimethylphenoxy)butan-1-one (0.330 g, 0.820 mmol) and dicyanozinc (0.116 g, 0.984 mmol) in DMF (1.50 mL) was added 1,1′-bis(diphenylphosphino)ferrocene (0.023 g, 0.041 mmol) and Pd2(dba)3 (0.038 g, 0.041 mmol). The vial was purged with argon, sealed, and heated at 120° C. for 16 h. The mixture was partitioned between EtOAc and water. The organic layer was washed with water and brine, dried over anhydrous MgSO4, filtered, and concentrated in vacuo to provide the crude material. The crude material was purified by flash chromatography (0-50% ethyl acetate:hexanes) to afford the title compound (0.246 g, 82% yield) as an off-white solid. LCMS, [M+H]+=349.1. 1H NMR (400 MHz, CDCl3) δ 7.41 (d, J=7.7 Hz, 1H), 7.28-7.17 (m, 2H), 7.01 (t, J=7.9 Hz, 1H), 6.75 (d, J=7.5 Hz, 1H), 6.64 (d, J=8.2 Hz, 1H), 3.96 (t, J=5.6 Hz, 2H), 3.82-3.71 (m, 2H), 2.85 (s, 2H), 2.73 (t, J=7.1 Hz, 2H), 2.24 (s, 3H), 2.18 (dt, J=12.9, 6.4 Hz, 2H), 2.05-1.88 (m, 5H).

Workup

  1. customThe vial was purged with argon
  2. customsealed
  3. customThe mixture was partitioned between EtOAc and water
  4. washThe organic layer was washed with water and brine
  5. dry with materialdried over anhydrous MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto provide the crude material
  9. customThe crude material was purified by flash chromatography (0-50% ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-4834f83a44854e28952dc8665367434a
Source dataset
uspto-grants-2015_06
Patent number
US09062028B2

Reaction notes

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