2-Bromobenzaldehyde → tert-butyl 1-(4-(1-oxo-3-phenyl-1H-inden-2-yl)phenyl)cyclobutylcarbamate

HRID 1037273Notes

Reaction equation

HRID 1037273 reaction equation
Br[C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].[C:10]1([C:16]#[C:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]3([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:27][CH2:26][CH2:25]3)=[CH:20][CH:19]=2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C([O-])(=O)C.[Na+]>O.[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[O:5]=[C:4]1[C:3]2[C:2](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:16]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[C:17]1[C:18]1[CH:23]=[CH:22][C:21]([C:24]2([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:33])([CH3:32])[CH3:34])[CH2:27][CH2:26][CH2:25]2)=[CH:20][CH:19]=1

Participants

7

Reactant 3

HCID 811292-BromobenzaldehydeHCID 517045Sodium AcetateHCID 57805483HCID 57805483, compound

Product 1

HCID 67067872tert-butyl 1-(4-(1-oxo-3-phenyl-1H-inden-2-yl)phenyl)cyclobutylcarbamateYield 6.2%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 16212273Tetrabutylammonium chloride hydrateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-bromobenzaldehyde (92.5 mg, 0.5 mmol), tert-butyl 1-(4-(phenylethynyl)phenyl)cyclobutylcarbamate (347 mg, 1.0 mmol), sodium acetate (164 mg, 2.0 mmol), tetrabutylammonium chloride hydrate (147.7 mg, 0.50 mmol) and palladium acetate (5.6 mg, 0.025 mmol) in DMF (10 mL) was heated at 100° C. for 48 h. The reaction mixture was concentrated to dryness and was partitioned between ethyl acetate (30 mL) and water (30 mL). The organic phase was washed with water (30 mL), brine (20 mL), dried (Na2SO4), filtered and concentrated in vacuo. The crude residue was purified by column chromatography (eluting with 10% ethyl acetate in hexane) to give title compound (14 mg, 6.2%). 1H NMR (500 MHz, CDCl3): 7.50 (d, 1H), 7.45-7.05 (m, 12H), 2.55-2.25 (m, 4H), 2.15-1.95 (m, 1H), 1.85-1.70 (m, 1H), 1.40-1.10 (br s, 9H).

Workup

  1. concentrationThe reaction mixture was concentrated to dryness
  2. customwas partitioned between ethyl acetate (30 mL) and water (30 mL)
  3. washThe organic phase was washed with water (30 mL), brine (20 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude residue was purified by column chromatography (eluting with 10% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-8c1da70ec0b04f49bb4ac33a2d980635
Source dataset
uspto-grants-2013_10
Patent number
US08546376B2

Reaction notes

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