Sodium Carbonate → HCID 86715487, compound

HRID 2284578Notes

Reaction equation

HRID 2284578 reaction equation
ClC1[C:7]([C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)NN=C3)=CC=CN=1.CC1C=C(B(O)O)C=CC=1.Br[C:28]1[C:33]([Cl:34])=[CH:32][CH:31]=[CH:30][N:29]=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:34][C:33]1[C:28]([C:15]2[CH:14]=[CH:10][CH:9]=[C:8]([CH3:7])[CH:16]=2)=[N:29][CH:30]=[CH:31][CH:32]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 27339503-Tolylboronic acidHCID 70163262-Bromo-3-chloropyridineHCID 867154695-(2-chloropyridin-3-yl)-1H-indazole2×

Product 1

HCID 86715487HCID 86715487, compoundYield 61%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

3-Chloro-2-(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 3-methylphenyl boronic acid (1.76 g, 12.9 mmol), 2-bromo-3-chloropyridine (2.7 g, 14.2 mmol), Pd(PPh3)4 (0.9 g, 0.77 mmol) and 2M aq. Na2CO3 (16 mL, 32 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-(3-methylphenyl)pyridine (1.62 g, 61%) as a clear liquid. 1H NMR (DMSO-d6): δ 8.60 (dd, 1H, J=1.4 and 4.7 Hz), 8.00 (dd, 1H, J=1.4 and 8.2 Hz), 7.44-7.37 (m, 3H), 7.25 (app d, 1H, J=8.2 Hz), 2.36 (s, 3H).LCMS: 97%, MS (m/e) 204.

Workup

  1. custom3-Chloro-2-(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-fad4098ac4f94cc5bbb168ce0a4284d3
Source dataset
uspto-grants-2015_09
Patent number
US09145433B2

Reaction notes

Loading…