Sodium Carbonate → HCID 86715486, compound

HRID 2284577Notes

Reaction equation

HRID 2284577 reaction equation
ClC1C(C2C=C3C(=CC=2)NN=C3)=CC=CN=1.[F:17][C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][C:19]=1[CH3:27].Br[C:29]1[C:34]([Cl:35])=[CH:33][CH:32]=[CH:31][N:30]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:35][C:34]1[C:29]([C:21]2[CH:22]=[CH:23][C:18]([F:17])=[C:19]([CH3:27])[CH:20]=2)=[N:30][CH:31]=[CH:32][CH:33]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 2774580(4-Fluoro-3-methylphenyl)boronic acidHCID 70163262-Bromo-3-chloropyridineHCID 867154695-(2-chloropyridin-3-yl)-1H-indazole2×

Product 1

HCID 86715486HCID 86715486, compoundYield 54.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

3-Chloro-2-(4-fluoro-3-methylphenyl)pyridine was synthesized analogous to the reaction conditions used in the preparation of 5-(2-chloropyridin-3-yl)-1H-indazole by heating the mixture of 4-fluoro-3-methylphenyl boronic acid (1.0 g, 6.5 mmol), 2-bromo-3-chloropyridine (1.4 g, 7.1 mmol), Pd(PPh3)4 (0.45 g, 0.38 mmol) and 2M aq. Na2CO3 (8 mL, 16 mmol) in 1,4-dioxane (125 mL) under argon atmosphere for 3 h. Upon work-up of the reaction mixture, as discussed in the preparation of 5-(2-chloropyridin-3-yl)-1H-indazole, the crude concentrate was purified by flash silica gel column chromatography [Combiflash® companion System® with RediSep® silica gel column 40 g, 10-30% EtOAC/hexanes eluting solvent gradient upon liquid loading on to column] to obtain 3-chloro-2-(4-fluoro-3-methylphenyl)pyridine as a white solid (790 mg, 54%). 1H NMR (DMSO-d6): δ 8.60 (dd, 1H, J=1.4 and 4.7 Hz), Hz), 8.02 (dd, 1H, J=1.4 and 8.2 Hz), 7.57 (app d, 1H, J=7.3 Hz), 7.54-7.49 (m, 1H), 7.42 (dd, 1H, J=4.7 and 8.2 Hz), 7.23 (t, 1H, J=8.8 Hz), 2.28 (s, 3H).LCMS: 97%, MS (m/e) 222.

Workup

  1. custom3-Chloro-2-(4-fluoro-3-methylphenyl)pyridine was synthesized analogous to the reaction conditions
  2. temperatureby heating
  3. concentrationthe crude concentrate
  4. customwas purified by flash silica gel column chromatography [Combiflash® companion System® with RediSep® silica gel column 40 g, 10-30% EtOAC/hexanes eluting solvent gradient upon liquid loading on to column]

Sources & evidence

ORD record
ord-30a5e92b23f5401a8f6045e7a81662c4
Source dataset
uspto-grants-2015_09
Patent number
US09145433B2

Reaction notes

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