Hydrochloric Acid → (3'-Fluoro-4-methyl-3,4'-bipyridin-2'-yl)(4-fluorophenyl)methanone

HRID 871150Notes

Reaction equation

HRID 871150 reaction equation
[F:1][C:2]1[C:3]([C:15]#N)=[N:4][CH:5]=[CH:6][C:7]=1[C:8]1[CH:9]=[N:10][CH:11]=[CH:12][C:13]=1[CH3:14].[F:17][C:18]1[CH:23]=[CH:22][C:21]([Mg]Br)=[CH:20][CH:19]=1.Cl.[OH-:27].[Na+]>C1COCC1.C(Cl)Cl.O>[F:1][C:2]1[C:3]([C:15]([C:21]2[CH:22]=[CH:23][C:18]([F:17])=[CH:19][CH:20]=2)=[O:27])=[N:4][CH:5]=[CH:6][C:7]=1[C:8]1[CH:9]=[N:10][CH:11]=[CH:12][C:13]=1[CH3:14]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 867304023-Fluoro-4-(4-methyl-3-pyridinyl)pyridine-2-carbonitrileHCID 178418676HCID 178418676, compound

Product 1

HCID 86730403(3'-Fluoro-4-methyl-3,4'-bipyridin-2'-yl)(4-fluorophenyl)methanoneYield 65.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3′-fluoro-4-methyl-3,4′-bipyridine-2′-carbonitrile (0.029 g, 0.136 mmol) in THF (Volume: 0.680 ml) cooled to 0° C. was added (4-fluorophenyl) magnesium bromide (0.170 ml, 0.340 mmol). The reaction mixture was allowed to stir at room temperature for 5 hr. Water and ice were carefully added, followed by acidification with 6 M HCl. After stirring for 20 min, CH2Cl2 was added and the pH was adjusted to 8.5 with aqueous 4 M NaOH. The layers were separated and the aqueous phase was extracted with CH2Cl2 (9×). The organics layers were combined, dried over Na2SO4, filtered, and concentrated to afford a residue. The crude material was dissolved in a minimal amount of CH2Cl2 to be chromatographed. Purification of the crude material by silica gel chromatography using an ISCO machine (12 g column, 30 mL/min, 70-90% EtOAc in hexanes over 14 min, tr=8 min) gave the title compound (29 mg, 0.089 mmol, 65.3% yield). ESI MS (M+H)+=311.1.

Workup

  1. stirringAfter stirring for 20 min
  2. customThe layers were separated
  3. extractionthe aqueous phase was extracted with CH2Cl2 (9×)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto afford a residue
  8. customto be chromatographed
  9. customPurification of the crude material by silica gel chromatography
  10. customan ISCO machine (12 g column, 30 mL/min, 70-90% EtOAc in hexanes over 14 min, tr=8 min)

Sources & evidence

ORD record
ord-9d7ab5641ea54b009e96a2d327bd68ba
Source dataset
uspto-grants-2015_03
Patent number
US08969586B2

Reaction notes

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