Cesium carbonate → HCID 11739863, compound

HRID 1831944Notes

Reaction equation

HRID 1831944 reaction equation
Br[C:2]1[C:3](=[O:26])[N:4]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([F:25])[CH:20]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17].[C:27]([O-])([O-])=O.[K+].[K+].C([O-])([O-])=O.[Cs+].[Cs+].CB1OB(C)OB(C)O1>O1CCOCC1.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:17][C:11]1[CH:12]=[C:13]([F:16])[CH:14]=[CH:15][C:10]=1[CH2:9][O:8][C:7]1[CH:6]=[CH:5][N:4]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([F:25])[CH:20]=2)[C:3](=[O:26])[C:2]=1[CH3:27]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 11430Potassium CarbonateHCID 574072TrimethylboroxineHCID 102165503-Bromo-4-[(2,4-difluorophenyl)methoxy]-1-[(3-fluorophenyl)methyl]-2(1H)-pyridinone

Product 1

HCID 11739863HCID 11739863, compoundYield 79%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 3-bromo-4-(2,4-difluorobenzyloxy)-1-(3-fluorobenzyl)-1H-pyridin-2-one (EXAMPLE 107) (0.14 g, 0.32 mmol), K2CO3 (88 mg, 0.64 mmol) and Cs2CO3 (0.10 g, 0.32 mmol) in dioxane (2 mL) was added Pd(PPh3)4 (18 mg, 0.12 mmol), followed by trimethylboroxine (40 mg, 0.32 mmol). The reaction mixture was degassed, purged with argon, and heated at reflux for 4 h. The reaction mixture was cooled to room temperature, and partitioned between water and EtOAc. The organic solution was washed with brine, dried (Na2SO4), filtered and concentrated under reduced pressure. Purification by flash column chromatography (silica, eluent methylene chloride to 97:3 methylene chloride/MeOH) afforded 4-(2,4-difluorobenzyloxy)-1-(3-fluorobenzyl)-3-methyl-1H-pyridin-2-one as a white solid (0.09 g, 79%): mp 127-129° C.; 1H NMR (300 MHz, CDCl3) δ 7.50-7.40 (m, 1H), 7.35-7.25 (m, 1H), 7.17 (d, J=9 Hz, 1H), 7.06 (d, J=6 Hz, 1H), 7.00-6.80 (m, 4H), 6.12 (d, J=9 Hz, 1H), 5.12 (s, 4H), 2.07 (s, 3H). ES HRMS m/z 360.1180 (M+H C20H16F3NO2 requires 360.1206).

Workup

  1. customThe reaction mixture was degassed
  2. custompurged with argon
  3. temperatureheated
  4. temperatureat reflux for 4 h
  5. custompartitioned between water and EtOAc
  6. washThe organic solution was washed with brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customPurification by flash column chromatography (silica, eluent methylene chloride to 97:3 methylene chloride/MeOH)

Sources & evidence

ORD record
ord-b589f70fa0be4c56827b83f4fff62f48
Source dataset
uspto-grants-2006_06
Patent number
US07067540B2

Reaction notes

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