Dichloromethane → HCID 66732034, compound

HRID 1963157Notes

Reaction equation

HRID 1963157 reaction equation
Cl[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6].[CH3:12][S:13]([C:16]1[CH:21]=[CH:20][C:19](B(O)O)=[CH:18][CH:17]=1)(=[O:15])=[O:14].C(=O)([O-])[O-].[K+].[K+].C(Cl)Cl>CO.Cl[Pd]Cl.O>[CH3:12][S:13]([C:16]1[CH:21]=[CH:20][C:19]([C:2]2[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=2)[C:5]([O:7][CH3:8])=[O:6])=[CH:18][CH:17]=1)(=[O:15])=[O:14]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 27343644-(Methanesulfonyl)phenylboronic acidHCID 2736842Methyl 2-chloropyridine-4-carboxylate

Product 1

HCID 66732034HCID 66732034, compoundYield 66.7%

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

Methyl 2-chloroisonicotinate (5 g, 29.14 mmol), 4-(methylsulfonyl)phenylboronic acid (7.58 g, 37.88 mmol), potassium carbonate (2.416 g, 17.48 mmol) and PdCl2 (dppf) (0.633 g, 0.87 mmol) were dissolved in methanol (30 mL) and divided up in two microwave vials. Each vial was heated to 100° C. in a single node microwave reactor for 35 min. DCM (250 mL) and water (250 mL) were added, shaken and the phases separated. The aqueous phase was extracted with DCM (250 mL). The combined organic phases were washed with brine (500 mL), dried with a phase separator and evaporated in vacuo. The residue was purified by automated flash chromatography on two Biotage® KP-SIL 340 g columns. A gradient of 20-70% EtOAc in heptane over 10 CV and then 70% EtOAc in heptane over 5 CV was used as mobile phase. The product was collected using the wavelength 253 nm. The product fractions were collected and evaporated in vacuo yielding methyl 2-(4-(methylsulfonyl)phenyl)-isonicotinate (5.66 g, 66.7%) as a white solid. 1H NMR (600 MHz, CDCl3) δ 3.09 (s, 3H), 3.98 (s, 3H), 7.85 (dd, 1H), 8.05 (d, 2H), 8.25 (d, 2H), 8.34 (s, 1H), 8.86 (t, 1H).

Workup

  1. customthe phases separated
  2. extractionThe aqueous phase was extracted with DCM (250 mL)
  3. washThe combined organic phases were washed with brine (500 mL)
  4. customdried with a phase separator
  5. customevaporated in vacuo
  6. customThe residue was purified by automated flash chromatography on two Biotage® KP-SIL 340 g columns
  7. customThe product was collected
  8. customThe product fractions were collected
  9. customevaporated in vacuo

Sources & evidence

ORD record
ord-f033ab15670e42cd8d1b08a5ade57101
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

Loading…