Triphenylphosphine → 4-[2-Methyl-5-(4-methylthiazol-2-yl)phenyl]-2,2,6,6-tetramethylpyran-3,5-dione

HRID 1470874Notes

Reaction equation

HRID 1470874 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([CH3:20])=[C:6]([CH:8]2[C:13](=[O:14])[C:12]([CH3:16])([CH3:15])[O:11][C:10]([CH3:18])([CH3:17])[C:9]2=[O:19])[CH:7]=1.[CH3:21][C:22]1[N:23]=[CH:24][S:25][CH:26]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(=O)([O-])[O-].[Ag+2].O.C(#N)C>[CH3:20][C:5]1[CH:4]=[CH:3][C:2]([C:24]2[S:25][CH:26]=[C:22]([CH3:21])[N:23]=2)=[CH:7][C:6]=1[CH:8]1[C:13](=[O:14])[C:12]([CH3:16])([CH3:15])[O:11][C:10]([CH3:18])([CH3:17])[C:9]1=[O:19]

Participants

6

Reactant 3

HCID 11776TriphenylphosphineHCID 127484-MethylthiazoleHCID 684842584-(5-Bromo-2-methylphenyl)-2,2,6,6-tetramethylpyran-3,5-dione

Product 1

HCID 684843724-[2-Methyl-5-(4-methylthiazol-2-yl)phenyl]-2,2,6,6-tetramethylpyran-3,5-dioneYield 17.1%

Reagents, catalysts & solvents 2

HCID 178418647HCID 178418647, compoundCatalystHCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
65 °C

Procedure

To a mixture of 4-(5-bromo-2-methylphenyl)-2,2,6,6-tetramethylpyran-3,5-dione (200 mg, 0.589 mmol), 4-methylthiazole (70 mg, 0.707 mmol), silver carbonate (814 mg, 2.94 mmol), triphenylphosphine (15 mg, 0.0589 mmol) and [1,1-bis(diphenylphosphino)-ferrocene]palladium(II)chloride (24 mg, 0.0294 mmol) is added a degassed solvent mixture of water/acetonitrile (1.5 ml, 1:1 ratio), followed by subsequent purging with nitrogen then heating at 65° C. for 65 hours with shaking. After cooling to room temperature the reaction mixture is then partitioned between 2M aqueous hydrochloric acid and dichloromethane, and the organic phase is separated. The aqueous layer is washed with a further aliquot of dichloromethane, and the combined organic layers are evaporated under reduced pressure to give a brown solid which is purified by preparative reverse phase HPLC to give 4-[2-methyl-5-(4-methylthiazol-2-yl)phenyl]-2,2,6,6-tetramethylpyran-3,5-dione as a pale yellow solid (36 mg).

Workup

  1. additionis added
  2. customby subsequent purging with nitrogen
  3. temperatureAfter cooling to room temperature the reaction mixture
  4. customis then partitioned between 2M aqueous hydrochloric acid and dichloromethane
  5. customthe organic phase is separated
  6. washThe aqueous layer is washed with a further aliquot of dichloromethane
  7. customthe combined organic layers are evaporated under reduced pressure
  8. customto give a brown solid which
  9. customis purified by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-53bdb44a9c0146b38371cbdbd26bbd72
Source dataset
uspto-grants-2015_04
Patent number
US09006429B2

Reaction notes

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