Water → HCID 10910237, compound

HRID 549445Notes

Reaction equation

HRID 549445 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][C:7]([CH3:13])([CH3:12])[C:8]2=[O:11])=[CH:4][CH:3]=1.[C:14]([Cu])#[N:15].CCOC(C)=O.O>CN1C(=O)CCC1>[CH3:12][C:7]1([CH3:13])[C:8](=[O:11])[C:9]2[C:5](=[CH:4][CH:3]=[C:2]([C:14]#[N:15])[CH:10]=2)[CH2:6]1

Participants

6

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 200820146-Bromo-2,2-dimethyl-2,3-dihydro-1H-inden-1-oneHCID 178418546HCID 178418546, compound

Product 1

HCID 10910237HCID 10910237, compoundYield 90%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A slurry of 6-bromo-2,2-dimethyl-2,3-dihydro-1H-inden-1-one (U.S. Pat. No. 5,401,758) (24.97 g, 0.104 mol) and CuCN (18.7 g, 0.208 mol) in NMP (160 mL) was heated at 175° C. for 4 h. After cooling to rt, the reaction mixture was poured into EtOAc (300 mL) and water (200 mL) with stirring. After 15 min, the solid was collected and the filter cake was rinsed with EtOAc (150 mL). The resulting two layers were separated and the aqueous portion was extracted with EtOAc (150 mL×3). The combined organic layer was washed with brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure to give a dark oil, which was divided into three portions and purified by flash chromatography on silica gel (120 g) eluting with EtOAc/Hexane mixtures to provide the title compound as a near colorless oil after concentration in vacuo (17.8 g, 90% yield). HPLC Ret. time: 2.55 min. LCMS MH+ (m/z) 186.31. 1H NMR: (DMSO-d6, 400 MHz): δ 8.13 (s, 1H), 8.11 (d, 1H), 7.78 (d, 1H), 3.10 (s, 2H), 1.15 (s, 6H).

Workup

  1. customthe solid was collected
  2. washthe filter cake was rinsed with EtOAc (150 mL)
  3. customThe resulting two layers were separated
  4. extractionthe aqueous portion was extracted with EtOAc (150 mL×3)
  5. washThe combined organic layer was washed with brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto give a dark oil, which
  10. custompurified by flash chromatography on silica gel (120 g)
  11. washeluting with EtOAc/Hexane

Sources & evidence

ORD record
ord-e709dcffcaeb47e7a61e828dc03e5ac1
Source dataset
uspto-grants-2011_05
Patent number
US07943658B2

Reaction notes

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