1,3-Dichloro-5-ethynylbenzene → 3-(3,5-Dichlorophenyl)-1-quinolin-3-ylprop-2-yn-1-one

HRID 1865418Notes

Reaction equation

HRID 1865418 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]#[CH:9])[CH:5]=[C:4]([Cl:10])[CH:3]=1.C([Li])CCC.CON(C)[C:19]([C:21]1[CH:22]=[N:23][C:24]2[C:29]([CH:30]=1)=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:20]>C1COCC1>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]#[C:9][C:19]([C:21]2[CH:22]=[N:23][C:24]3[C:29]([CH:30]=2)=[CH:28][CH:27]=[CH:26][CH:25]=3)=[O:20])[CH:5]=[C:4]([Cl:10])[CH:3]=1

Participants

5

Reactant 3

HCID 138235471,3-Dichloro-5-ethynylbenzeneHCID 15837794N-methoxy-N-methylquinoline-3-carboxamideHCID 178418339Butyllithium

Product 1

HCID 685677233-(3,5-Dichlorophenyl)-1-quinolin-3-ylprop-2-yn-1-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of the 1,3-dichloro-5-ethynylbenzene (200 mg, 1.16 mmol) in anhydrous THF cooled to −78° C. under a N2 atmosphere was added nButLi (800 μL, 1.28 mmol). After 5 minutes a solution of the intermediate from step A (380 mg, 1.75 mmol) in THF (3 mL) was added. The reaction was gradually warmed to room temperature over 30 minutes and quenched with saturated NH4Cl solution. The resulting bi-phasic mixture was extracted with ethyl acetate, washed with saturated NaCl solution, dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography using 15% ethyl acetate-hexanes to afford the product as a light yellow solid. 1H NMR (CDCl3, 500 MHz): 9.63 (s, J=2.1 Hz, 1H), 8.96 (d, J=1.6 Hz, 1H), 8.24 (d, J=8.5 Hz, 1H), 8.07 (d, J=8.3 Hz, 1H), 7.94 (t, J=8.0 Hz, 1H), 7.73 (t, J=7.8 Hz, 1H), 7.64 (d, J=1.8 Hz, 2H), 7.55 (t, J=2.0 Hz, 1H). LC-MS: 3.99 min; (M+H)=326.0.

Workup

  1. customquenched with saturated NH4Cl solution
  2. extractionThe resulting bi-phasic mixture was extracted with ethyl acetate
  3. washwashed with saturated NaCl solution
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-5ff3a7e662104cbbb940bcea6a7fff8b
Source dataset
uspto-grants-2009_12
Patent number
US07625938B2

Reaction notes

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