Potassium Phosphate, Tribasic → 4-[5-(3,5-Dichloropyridin-2-yl)-2-methylphenyl]-2,2,6,6-tetramethylpyran-3,5-dione

HRID 1191565Notes

Reaction equation

HRID 1191565 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[CH:4][C:3]=1[CH:11]1[C:16](=[O:17])[C:15]([CH3:19])([CH3:18])[O:14][C:13]([CH3:21])([CH3:20])[C:12]1=[O:22].Br[C:24]1[C:29]([Cl:30])=[CH:28][C:27]([Cl:31])=[CH:26][N:25]=1.[Na].[Na].[Na].S(C1C=C(P(C2C=CC=C(S(O)(=O)=O)C=2)C2C=CC=C(S(O)(=O)=O)C=2)C=CC=1)(O)(=O)=O.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C(#N)C>[Cl:30][C:29]1[C:24]([C:5]2[CH:6]=[CH:7][C:2]([CH3:1])=[C:3]([CH:11]3[C:16](=[O:17])[C:15]([CH3:19])([CH3:18])[O:14][C:13]([CH3:21])([CH3:20])[C:12]3=[O:22])[CH:4]=2)=[N:25][CH:26]=[C:27]([Cl:31])[CH:28]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 8170902-Bromo-3,5-dichloropyridineHCID 684880184-Methyl-3-(2,2,6,6-tetramethyl-3,5-dioxo-tetrahydropyran-4-yl)phenylboronic acidHCID 86657037CID 86657037

Product 1

HCID 684845354-[5-(3,5-Dichloropyridin-2-yl)-2-methylphenyl]-2,2,6,6-tetramethylpyran-3,5-dioneYield 42.3%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

To a microwave vial is added 4-methyl-3-(2,2,6,6-tetramethyl-3,5-dioxo-tetrahydropyran-4-yl)phenylboronic acid (200 mg, 0.657 mmol), 2-bromo-3,5-dichloropyridine (149 mg, 0.657 mmol), palladium acetate (3.7 mg, 0.0164 mmol), tris(3-sulfophenyl)phosphine trisodium salt (22 mg, 0.0394 mmol) and potassium phosphate (697 mg, 3.28 mol), followed by a degassed solvent mixture of water/acetonitrile (1.6 ml, 2:1 ratio). The mixture is flushed with nitrogen then stirred at ambient temperature for 5 minutes before heating at 160° C. under microwave irradiation for 15 minutes. After cooling to room temperature the reaction is partitioned between 2M aqueous hydrochloric acid and dichloromethane, and the organic phase is separated. The aqueous phase is further extracted with dichloromethane and all organic fractions are combined then evaporated. The residue is purified by preparative reverse phase HPLC to give 4-[5-(3,5-dichloropyridin-2-yl)-2-methylphenyl]-2,2,6,6-tetramethylpyran-3,5-dione (113 mg).

Workup

  1. customThe mixture is flushed with nitrogen
  2. temperaturebefore heating at 160° C. under microwave irradiation for 15 minutes
  3. temperatureAfter cooling to room temperature the reaction
  4. customis partitioned between 2M aqueous hydrochloric acid and dichloromethane
  5. customthe organic phase is separated
  6. extractionThe aqueous phase is further extracted with dichloromethane
  7. customall organic fractions are combined then evaporated
  8. customThe residue is purified by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-5118f8d3c7e54a30bca03a08c3c78d20
Source dataset
uspto-grants-2014_03
Patent number
US08680012B2

Reaction notes

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