(3-Methoxyphenyl)boronic acid → 1-(2,6-Difluorobenzyl)-2,6-dimethyl-3-(3-methoxyphenyl)-5-formyl-4-pyridone

HRID 495524Notes

Reaction equation

HRID 495524 reaction equation
[F:1][C:2]1[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[C:3]=1[CH2:4][N:5]1[C:10]([CH3:11])=[C:9]([CH:12]=[O:13])[C:8](=[O:14])[C:7](Br)=[C:6]1[CH3:16].[CH3:22][O:23][C:24]1[CH:25]=[C:26](B(O)O)[CH:27]=[CH:28][CH:29]=1>C1C=CC=CC=1.C(O)C.COCCOC.[OH-].[Ba+2].[OH-].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:1][C:2]1[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[C:3]=1[CH2:4][N:5]1[C:10]([CH3:11])=[C:9]([CH:12]=[O:13])[C:8](=[O:14])[C:7]([C:28]2[CH:27]=[CH:26][CH:25]=[C:24]([O:23][CH3:22])[CH:29]=2)=[C:6]1[CH3:16]

Participants

6

Reactant 2

HCID 2734370(3-Methoxyphenyl)boronic acidHCID 223272251-(2,6-Difluorobenzyl)-2,6-dimethyl-3-bromo-5-formyl-4-pyridone

Product 1

HCID 223272511-(2,6-Difluorobenzyl)-2,6-dimethyl-3-(3-methoxyphenyl)-5-formyl-4-pyridoneYield 42.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6093286Barium hydroxideSolventHCID 86588578Benzene ethanol 1,2-dimethoxyethaneSolvent

Procedure

1-(2,6-Difluorobenzyl)-2,6-dimethyl-3-bromo-5-formyl-pyrid-4-one (1.36 g, 3.8 mmol) stirred with 3-methoxyphenyl boronic acid (696 mg, 4.6 mmol) and tetrakis(triphenylphosphine)palladium(0) (439 mg, 380 μmol) in benzene/ethanol/DME (76 ml, 10/1/11) and barium hydroxide (30 mL, sat., aq.) under N2 at 90° C., protected from light over 8 hours. The organic layer was then concentrated and purified using flash silica chromatography (ethyl acetate/hexane-1/9), giving the product as a cream-colored solid (622 mg, 1.6 mmol, 42% yield). 1H NMR (CDCl3, 300 MHz) δ 10.55 (s, 1H), 7.41-7.31 (m, 2H), 7.00-6.74 (m, 5H), 5.35 (s, 2H), 3.81 (s, 3H), 2.79 (s, 3H), 2.25 (s, 3H); MS: 384 (MH+).

Workup

  1. concentrationThe organic layer was then concentrated
  2. custompurified

Sources & evidence

ORD record
ord-3f1c57e491ac4107978e2d3656434e6b
Source dataset
uspto-grants-2005_09
Patent number
US06939883B2

Reaction notes

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