Hydrochloric Acid → HCID 178526696, compound

HRID 575620Notes

Reaction equation

HRID 575620 reaction equation
Cl[C:2]1[CH:7]=[C:6]([F:8])[C:5]([C:9]2[CH:14]=[C:13]([N+:15]([O-:17])=[O:16])[CH:12]=[CH:11][C:10]=2[O:18][C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[CH:4][N:3]=1.[OH-:27].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.Cl>O1CCOCC1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CCOC(C)=O>[F:26][C:20]1[CH:21]=[C:22]([F:25])[CH:23]=[CH:24][C:19]=1[O:18][C:10]1[CH:11]=[CH:12][C:13]([N+:15]([O-:17])=[O:16])=[CH:14][C:9]=1[C:5]1[C:6]([F:8])=[CH:7][C:2]([OH:27])=[N:3][CH:4]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 1180223532-Chloro-5-[2-(2,4-difluorophenoxy)-5-nitrophenyl]-4-fluoropyridine

Product 1

HCID 178526696HCID 178526696, compound

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-chloro-5-[2-(2,4-difluorophenoxy)-5-nitrophenyl]-4-fluoropyridine (140 mg, 0.37 mmol), KOH (62 mg, 1.11 mmol), Pd2(dba)3 (17 mg, 5%), and XPhos (18 mg, 10%) was suspended in 1,4-dioxane (1.9 mL) and water (316 μL). After purging the reaction vial with nitrogen for 5 min, the capped vial was stirred at 100° C. for 1 h. After the mixture cooled to rt, it was treated with 1N HCl (aq) (1 mL) and EtOAc (5 mL). The biphasic mixture was filtered through a short plug of celite and the celite plug was washed with EtOAc (˜50 mL). The filtrate was washed with water (2×30 mL), brine, dried over sodium sulfate, filtered and concentrated in vacuo to afford a orange solid, 5-[2-(2,4-difluorophenoxy)-5-nitrophenyl]-4-fluoropyridin-2-ol (LCMS (M+H)+=363). After the solid was diluted with DMF (2.4 mL), it was treated with K2CO3 (112 mg) and MeI (23 μL). After stirring at rt for 5 h, the mixture was treated with water (10 mL) and extracted with EtOAc (3×10 mL); the combined organic extracts were washed with saturated bicarbonate solution (aq), dried over sodium sulfate, filtered, concentrated in vacuo. The resulting residue was purified by silica gel column chromatography (4 g ISCO, gradient 05-95% EtOAc in hexanes) to afford the desired product, 5-[2-(2,4-difluorophenoxy)-5-nitrophenyl]-4-fluoro-1-methylpyridin-2-one as a tan solid (95 mg). LCMS (M+H)+=377.

Workup

  1. customAfter purging
  2. customthe reaction vial with nitrogen for 5 min
  3. temperatureAfter the mixture cooled to rt
  4. filtrationThe biphasic mixture was filtered through a short plug of celite
  5. washthe celite plug was washed with EtOAc (˜50 mL)
  6. washThe filtrate was washed with water (2×30 mL), brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a169d03d59c445ee9a934fd167f20940
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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