1,2-Dimethoxyethane → HCID 86702174, compound

HRID 2172724Notes

Reaction equation

HRID 2172724 reaction equation
B(O)O.[F:4][C:5]1[CH:25]=[CH:24][C:8]([O:9][C:10]2[CH:15]=[CH:14][C:13](CC(C(O)(C)C)(C)O)=[CH:12][CH:11]=2)=[CH:7][CH:6]=1.Cl[C:27]1[CH:32]=[C:31]([Cl:33])[CH:30]=[C:29]([Cl:34])[N:28]=1.C(=O)([O-])[O-].[Na+].[Na+].C(COC)OC>O.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.C(O)C>[Cl:34][C:29]1[CH:30]=[C:31]([Cl:33])[CH:32]=[C:27]([C:13]2[CH:12]=[CH:11][C:10]([O:9][C:8]3[CH:7]=[CH:6][C:5]([F:4])=[CH:25][CH:24]=3)=[CH:15][CH:14]=2)[N:28]=1

Participants

8

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 27665Pyridine, 2,4,6-trichloro-2×HCID 178459198HCID 178459198, compound2×

Product 1

HCID 86702174HCID 86702174, compound

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
80 °C

Procedure

As described in Scheme 7, in a 50-mL vial with a screw-top septum, 4-(4′-fluorophenoxy)phenyl pinacol boronate (compound A) (3 g, 9.55 mmol) was reacted with 2,4,6-trichloropyridine (compound B) (1.73 grams, 9.55 mmol, Sigma Aldrich), sodium carbonate (2 g, 19.1 mmol), and PdCl2(PPh3)2 (335 mg, 0.48 mmol, Sigma Aldrich), in a 20-mL solution of 2 parts dimethoxyethane, 1 part ethanol, and 2 parts water. The reaction mixture was heated to 80° C. overnight. When the reaction was complete as indicated by LC/MS, the mixture was diluted with water (100 mL) and extracted with ethyl acetate (2×100 mL). The organic layers were combined, dried over sodium sulfate, and concentrated. The residue was chromatographed by CombiFlash® (220-gram silica gel, 0-100% EtOAc/Hexane) to provide 2,4-dichloro-6-[4-(4-fluoro-phenoxy)-phenyl]-pyridine (compound C) as a waxy solid (1 g, 3 mmol). 1H NMR (CHCl3): 7.97-7.92 (m, 2 H), 7.60-7.57 (m, 1 H), 7.27-7.24 (m, 1 H), 7.11-6.99 (m, 6H). LC/MS: m/z 333.

Workup

  1. extractionextracted with ethyl acetate (2×100 mL)
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated
  4. customThe residue was chromatographed by CombiFlash® (220-gram silica gel, 0-100% EtOAc/Hexane)

Sources & evidence

ORD record
ord-9d9d4c1f37c642d8a7bad5a5644b0405
Source dataset
uspto-grants-2015_06
Patent number
US09056832B2

Reaction notes

Loading…