Cesium carbonate → HCID 66799594, compound

HRID 2172725Notes

Reaction equation

HRID 2172725 reaction equation
[F:1][C:2]1[CH:23]=[CH:22][C:5]([O:6][C:7]2[CH:8]=[C:9](B3OC(C)(C)C(C)(C)O3)[CH:10]=[CH:11][CH:12]=2)=[CH:4][CH:3]=1.B([O-])[O-].[CH2:27]([O:29][C:30]([C:32]1[CH:37]=[C:36]([Cl:38])[CH:35]=[C:34](Cl)[N:33]=1)=[O:31])[CH3:28].C(=O)([O-])[O-].[Cs+].[Cs+]>COCCOC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O.CCO>[CH2:27]([O:29][C:30]([C:32]1[CH:37]=[C:36]([Cl:38])[CH:35]=[C:34]([C:9]2[CH:10]=[CH:11][CH:12]=[C:7]([O:6][C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:23][CH:22]=3)[CH:8]=2)[N:33]=1)=[O:31])[CH3:28]

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 52982911Ethyl 4,6-dichloropyridine-2-carboxylateHCID 66799740HCID 66799740, compoundHCID 178514824HCID 178514824, compound

Product 1

HCID 66799594HCID 66799594, compound

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

In a 50-ml vial with a screw-top septum, 2-[3-(4-fluoro-phenoxy)-phenyl]-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (0.500 g, 1.59 mmol) was dissolved in 6 ml DME, 3 ml EtOH, and 6 ml water. The boronate was then treated with one equivalent of 4,6-dichloro-pyridine-2-carboxylic acid ethyl ester (Anichem), PdCl2(PPh3)2 (0.078 g, 0.11 mmol), and cesium carbonate (1.04 g, 3.18 mmol). The vial was purged with argon and heated to 90° C. for 10 hours, at which time the reaction was complete. The reaction mixture was diluted with 50 ml water and the aqueous layer acidified with about 10 ml 4N aq. HCl. The desired material was extracted with EtOAc (2×50 ml). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by combiflash using a 40-gram silica column and a gradient of EtOAc (100% max) in hexane to provide 0.445 g of 4-chloro-6-[3-(4-fluoro-phenoxy)-phenyl]-pyridine-2-carboxylic acid ethyl ester.

Workup

  1. customThe vial was purged with argon
  2. additionThe reaction mixture was diluted with 50 ml water
  3. extractionThe desired material was extracted with EtOAc (2×50 ml)
  4. dry with materialThe combined organic layers were dried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by combiflash

Sources & evidence

ORD record
ord-840257d56b454788b6a2b041cf083521
Source dataset
uspto-grants-2015_06
Patent number
US09056832B2

Reaction notes

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