2-Bromo-2-methylpropanoyl cyanide → 5-(4-methoxyphenyl)-2,2-dimethyl-4-(4-(quinolin-2-ylmethoxy)phenyl)furan-3(2H)-one

HRID 1776305Notes

Reaction equation

HRID 1776305 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9](=[O:29])[CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]3[CH:28]=[CH:27][C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[N:20]=3)=[CH:13][CH:12]=2)=[CH:5][CH:4]=1.Br[C:31]([CH3:37])([CH3:36])[C:32](C#N)=[O:33]>C1COCC1.CC([O-])(C)C.[K+]>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[O:29][C:31]([CH3:37])([CH3:36])[C:32](=[O:33])[C:10]=2[C:11]2[CH:12]=[CH:13][C:14]([O:17][CH2:18][C:19]3[CH:28]=[CH:27][C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[N:20]=3)=[CH:15][CH:16]=2)=[CH:5][CH:4]=1

Participants

5

Reactant 2

HCID 124878382-Bromo-2-methylpropanoyl cyanideHCID 593548091-(4-Methoxyphenyl)-2-(4-(quinolin-2-ylmethoxy)phenyl)ethanone

Product 1

HCID 445944685-(4-methoxyphenyl)-2,2-dimethyl-4-(4-(quinolin-2-ylmethoxy)phenyl)furan-3(2H)-oneYield 8.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 23665647Potassium tert-butoxideSolvent

Procedure

To a room temperature, stirred solution of 1-(4-methoxyphenyl)-2-(4-(quinolin-2-ylmethoxy)phenyl)ethanone (100 mg, 0.26 mmol) in THF (5 mL), t-BuOK (1.0 mL, 1.0 N solution in THF) was added under an inert atmosphere and the resulting mixture was stirred for 30 min. 2-Bromo-2-methylpropanoyl cyanide (90 mg, 0.5 mmol) was then added to the reaction mixture and stirring was continued for an additional 16 h. The reaction mixture was quenched with cold water (10 mL) and extracted with EtOAc (2×50 mL). The combined organic layers were washed with water (30 mL) and brine (30 mL), dried over Na2SO4, filtered, concentrated and purified by column chromatography (10-15% ethyl acetate in hexanes) to afford 5-(4-methoxyphenyl)-2,2-dimethyl-4-(4-(quinolin-2-ylmethoxy)phenyl)furan-3(2H)-one (10 mg) as a solid.

Workup

  1. additionwas added under an inert atmosphere
  2. stirringstirring
  3. waitwas continued for an additional 16 h
  4. customThe reaction mixture was quenched with cold water (10 mL)
  5. extractionextracted with EtOAc (2×50 mL)
  6. washThe combined organic layers were washed with water (30 mL) and brine (30 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. custompurified by column chromatography (10-15% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-a384759bd5a7443dad538e1ac69276b9
Source dataset
uspto-grants-2016_02
Patent number
US09265767B2

Reaction notes

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