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

HRID 871154Notes

Reaction equation

HRID 871154 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].[C:17]1([Mg]Br)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.Cl.[OH-:26].[Na+]>C1COCC1.C(Cl)Cl.O>[F:1][C:2]1[C:3]([C:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:26])=[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 178418255HCID 178418255, compound

Product 1

HCID 86730408(3'-Fluoro-4-methyl-3,4'-bipyridin-2'-yl)(phenyl)methanoneYield 64.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3′-fluoro-4-methyl-3,4′-bipyridine-2′-carbonitrile (0.027 g, 0.127 mmol) in THF (Volume: 0.633 ml) cooled to 0° C. was added phenylmagnesium bromide (0.317 ml, 0.317 mmol). The reaction mixture was allowed to stir at room temperature overnight. 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 and 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, 70-100% EtOAc in hexanes over 19 min, tr=6.5 min) gave the title compound (0.025 g, 0.081 mmol, 64.2% yield) as an orange residue. ESI MS (M+H)+=293.1.

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, 70-100% EtOAc in hexanes over 19 min, tr=6.5 min)

Sources & evidence

ORD record
ord-f8cdeb17fecb4082b0b28583392e470d
Source dataset
uspto-grants-2015_03
Patent number
US08969586B2

Reaction notes

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