Hydrochloric Acid → (5-Fluoro-2-methoxyphenyl)(3'-fluoro-4-methyl-3,4'-bipyridin-2'-yl)methanone

HRID 593753Notes

Reaction equation

HRID 593753 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:19]=[CH:20][C:21]([O:26][CH3:27])=[C:22]([Mg]Br)[CH:23]=1.Cl.[OH-:29].[Na+]>C1COCC1.C(Cl)Cl.O>[F:17][C:18]1[CH:19]=[CH:20][C:21]([O:26][CH3:27])=[C:22]([C:15]([C:3]2[C:2]([F:1])=[C:7]([C:8]3[CH:9]=[N:10][CH:11]=[CH:12][C:13]=3[CH3:14])[CH:6]=[CH:5][N:4]=2)=[O:29])[CH:23]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 867304023-Fluoro-4-(4-methyl-3-pyridinyl)pyridine-2-carbonitrileHCID 178491810HCID 178491810, compound

Product 1

HCID 86730410(5-Fluoro-2-methoxyphenyl)(3'-fluoro-4-methyl-3,4'-bipyridin-2'-yl)methanoneYield 48%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3′-fluoro-4-methyl-3,4′-bipyridine-2′-carbonitrile (0.031 g, 0.145 mmol) in THF (Volume: 0.727 ml) cooled to 0° C. was added (5-fluoro-2-methoxyphenyl)magnesium bromide (0.727 ml, 0.363 mmol). The reaction mixture was allowed to stir at room temperature. Water and ice were carefully added, followed by acidification with 6 M HCl. After stirring for 1 hr, CH2Cl2 was added and the pH was adjusted to 8.5 with aqueous 4 M NaOH. The layers were separated. The aqueous phase was extracted with CH2Cl2 (5×). Organics combined, dried over Na2SO4, filtered, and concentrated to afford a purple 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 (4 g column, 18 mL/min, 60-100% EtOAc in hexanes over 18 min, tr=9 min) gave the title compound (0.024 g, 0.070 mmol, 48.0% yield) as an orange residue. ESI MS (M+H)+=340.2.

Workup

  1. stirringAfter stirring for 1 hr
  2. customThe layers were separated
  3. extractionThe aqueous phase was extracted with CH2Cl2 (5×)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto afford a purple residue
  8. customto be chromatographed
  9. customPurification of the crude material by silica gel chromatography
  10. customan ISCO machine (4 g column, 18 mL/min, 60-100% EtOAc in hexanes over 18 min, tr=9 min)

Sources & evidence

ORD record
ord-fd525c67c16c4c4cb788b6b32c4dd4d3
Source dataset
uspto-grants-2016_01
Patent number
US09242967B2

Reaction notes

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