Sodium hydride → 7-Bromo-3-(4-methoxybenzyl)-3,7b-dihydro-1H-cyclopropa[c]quinolin-2(1aH)-one

HRID 2175213Notes

Reaction equation

HRID 2175213 reaction equation
[H-].[Na+].[I-].[CH3:4][S+](C)(C)=O.[Br:9][C:10]1[CH:19]=[CH:18][CH:17]=[C:16]2[C:11]=1[CH:12]=[CH:13][C:14](=[O:29])[N:15]2[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=1>CS(C)=O>[Br:9][C:10]1[C:11]2[CH:12]3[CH2:4][CH:13]3[C:14](=[O:29])[N:15]([CH2:20][C:21]3[CH:22]=[CH:23][C:24]([O:27][CH3:28])=[CH:25][CH:26]=3)[C:16]=2[CH:17]=[CH:18][CH:19]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 709830295-Bromo-1-(4-methoxybenzyl)quinolin-2(1H)-one

Product 1

HCID 867125757-Bromo-3-(4-methoxybenzyl)-3,7b-dihydro-1H-cyclopropa[c]quinolin-2(1aH)-oneYield 46.1%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

To a suspension of sodium hydride (136 mg, 3.40 mmol) in DMSO (5 mL) at room temperature was added trimethylsulfoxonium iodide (661 mg, 3.00 mmol) slowly under nitrogen. The reaction mixture was stirred at room temperature for 1 h, and then 5-bromo-1-(4-methoxybenzyl)quinolin-2(1H)-one (689 mg, 2.00 mmol) in 1 mL DMSO was added. Upon completion of addition, the reaction mixture was stirred at room temperature for 2 h, and then heated to 90° C. for 2 d. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The combined organic layer was washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated. The resulting residue was purified by flash chromatography (0 to 30% ethyl acetate:hexanes) to afford the title compound (330 mg, 45% yield) as a white powder. LCMS, [M+H]+=358.0. 1H NMR (400 MHz, CDCl3) δ 7.21 (d, J=7.7 Hz, 1H), 7.08 (d, J=8.2 Hz, 2H), 6.91 (t, J=8.0 Hz, 1H), 6.85-6.75 (m, 3H), 4.97-5.25 (m, 2H), 3.75 (s, 3H), 2.90 (td, J=8.1, 5.2 Hz, 1H), 2.40 (ddd, J=9.6, 8.0, 4.9 Hz, 1H), 1.74 (td, J=9.1, 4.4 Hz, 1H), 0.69 (q, J=4.8 Hz, 1H).

Workup

  1. additionUpon completion of addition
  2. stirringthe reaction mixture was stirred at room temperature for 2 h
  3. temperatureheated to 90° C. for 2 d
  4. temperatureAfter cooling to room temperature
  5. customthe reaction mixture was quenched with water
  6. extractionextracted with EtOAc
  7. washThe combined organic layer was washed with brine
  8. dry with materialdried over anhydrous Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe resulting residue was purified by flash chromatography (0 to 30% ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-078d55f8e0674e70b943c0486ae41e3d
Source dataset
uspto-grants-2015_06
Patent number
US09062028B2

Reaction notes

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