2-Bromoethanol → (4-Cyclopropyl-3,4-dihydro-2H-quinoxalin-1-yl)-{4-[2,5-dichloro-4-(2-hydroxy-ethoxy)-phenoxy]-pyridin-3-yl}-methanone

HRID 1025885Notes

Reaction equation

HRID 1025885 reaction equation
[CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[N:7]([C:14]([C:16]3[CH:17]=[N:18][CH:19]=[CH:20][C:21]=3[O:22][C:23]3[CH:28]=[C:27]([Cl:29])[C:26]([OH:30])=[CH:25][C:24]=3[Cl:31])=[O:15])[CH2:6][CH2:5]2)[CH2:3][CH2:2]1.[H-].[Na+].Br[CH2:35][CH2:36][OH:37]>CN(C)C=O>[CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[N:7]([C:14]([C:16]3[CH:17]=[N:18][CH:19]=[CH:20][C:21]=3[O:22][C:23]3[CH:28]=[C:27]([Cl:29])[C:26]([O:30][CH2:35][CH2:36][OH:37])=[CH:25][C:24]=3[Cl:31])=[O:15])[CH2:6][CH2:5]2)[CH2:2][CH2:3]1

Participants

5

Reactant 3

HCID 108982-BromoethanolHCID 24758Sodium hydrideHCID 53311358(4-Cyclopropyl-3,4-dihydro-2H-quinoxalin-1-yl)-[4-(2,5-dichloro-4-hydroxy-phenoxy)-pyridin-3-yl]-methanone

Product 1

HCID 53311446(4-Cyclopropyl-3,4-dihydro-2H-quinoxalin-1-yl)-{4-[2,5-dichloro-4-(2-hydroxy-ethoxy)-phenoxy]-pyridin-3-yl}-methanoneYield 46%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 0.15 g (0.33 mmol) (4-cyclopropyl-3,4-dihydro-2H-quinoxalin-1-yl)-[4-(2,5-dichloro-4-hydroxy-phenoxy)-pyridin-3-yl]-methanone (Example 57) in 2 mL N,N-dimethylformamide was added 0.016 g (0.37 mmol) sodium hydride (60% dispersion in mineral oil, Aldrich). The reaction mixture was stirred for 15 min. at room temperature before 0.03 mL (0.36 mmol) 2-bromoethanol (commercially available, CAS RN 540-51-2) were added. After stirring for 3 hours at room temperature another 0.03 mL (0.36 mmol) 2-bromoethanole were added. After 72 hours the reaction mixture was poured on water and was extracted three times with ethyl acetate. The organic layers were washed with water and brine, dried over magnesium sulfate, filtered, treated with silica gel and evaporated. The resulting powder was purified by silica gel chromatography using a MPLC system (20 g silica gel column, CombiFlash Companion, Isco Inc.) with a gradient of n-heptane:ethyl acetate (100:0 to 25:75) to give 0.075 g (46%) of the title compound as a light brown foam. MS (ESI): m/z=500.113 [M+H]+.

Workup

  1. additionwere added
  2. addition2-bromoethanole were added
  3. additionAfter 72 hours the reaction mixture was poured on water
  4. extractionwas extracted three times with ethyl acetate
  5. washThe organic layers were washed with water and brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. additiontreated with silica gel
  9. customevaporated
  10. customThe resulting powder was purified by silica gel chromatography

Sources & evidence

ORD record
ord-dfcaaafb9887412696a5de87a57415df
Source dataset
uspto-grants-2014_05
Patent number
US08729091B2

Reaction notes

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