(R)-3-(4-Bromo-phenyl)-1-(2-methyl-pyridin-4-yl)-3-o-tolyl-propan-1-one → HCID 66668285, compound

HRID 1617989Notes

Reaction equation

HRID 1617989 reaction equation
[I-].[C:2]([O:6][C:7]([N:9]1[CH2:14][CH2:13][CH:12]([Zn+])[CH2:11][CH2:10]1)=[O:8])([CH3:5])([CH3:4])[CH3:3].Br[C:17]1[CH:22]=[CH:21][C:20]([C@H:23]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=2[CH3:40])[CH2:24][C:25]([C:27]2[CH:32]=[CH:31][N:30]=[C:29]([CH3:33])[CH:28]=2)=[O:26])=[CH:19][CH:18]=1>CN(C)C(=O)C.[Cu]I.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].ClCCl>[CH3:33][C:29]1[CH:28]=[C:27]([C:25](=[O:26])[CH2:24][C@H:23]([C:20]2[CH:21]=[CH:22][C:17]([CH:12]3[CH2:13][CH2:14][N:9]([C:7]([O:6][C:2]([CH3:5])([CH3:4])[CH3:3])=[O:8])[CH2:10][CH2:11]3)=[CH:18][CH:19]=2)[C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=2[CH3:40])[CH:32]=[CH:31][N:30]=1

Participants

6

Reactant 2

HCID 66666695(R)-3-(4-Bromo-phenyl)-1-(2-methyl-pyridin-4-yl)-3-o-tolyl-propan-1-oneHCID 178452044HCID 178452044, compound

Product 1

HCID 66668285HCID 66668285, compoundYield 57%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418807HCID 178418807, compoundCatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
85 °C

Procedure

(1-(tert-Butoxycarbonyl)piperidin-4-yl) zinc(II) iodide solution (0.5 M in N,N-dimethylacetamide, 2.0 mL, 1.0 mmol; preparation according to J. Org. Chem. 2004, 69, 5120) was added at room temperature under argon to a mixture of (R)-3-(4-bromophenyl)-1-(2-methylpyridin-4-yl)-3-o-tolylpropan-1-one (example 142, step 2; 200 mg, 507 μmol), copper(I) iodide (9.7 mg, 51 μmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane adduct (18.6 mg, 25.4 μmol) in N,N-dimethylacetamide (3 mL). The reaction mixture was heated at 85° C., then after 4 h partitioned between sat. aq. ammonium chloride solution and ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered, and evaporated. Chromatography (SiO2; heptane-ethyl acetate gradient) produced the title compound (144 mg, 57%). Off-white foam, MS (ESI+): m/z=499.3 ([M+H]+).

Workup

  1. customafter 4 h partitioned between sat. aq. ammonium chloride solution and ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated

Sources & evidence

ORD record
ord-be294fec3cab40aea3896840fb1f625a
Source dataset
uspto-grants-2014_07
Patent number
US08765730B2

Reaction notes

Loading…