Sodium Carbonate → HCID 66835064, compound

HRID 536280Notes

Reaction equation

HRID 536280 reaction equation
Cl[C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([N:11]([CH3:13])[CH3:12])[N:10]=1)[C:5]([OH:7])=[O:6].[C:14]([O:18][C:19]([C:21]1[CH:26]=[CH:25][C:24](B(O)O)=[CH:23][CH:22]=1)=[O:20])([CH3:17])([CH3:16])[CH3:15].C(=O)([O-])[O-].[Na+].[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[C:14]([O:18][C:19]([C:21]1[CH:26]=[CH:25][C:24]([C:2]2[CH:3]=[C:4]([CH:8]=[C:9]([N:11]([CH3:13])[CH3:12])[N:10]=2)[C:5]([OH:7])=[O:6])=[CH:23][CH:22]=1)=[O:20])([CH3:17])([CH3:15])[CH3:16]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 2773301(4-((Tert-butoxy)carbonyl)phenyl)boronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 214303542-Chloro-6-(dimethylamino)isonicotinic acid

Product 1

HCID 66835064HCID 66835064, compoundYield 65.5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

2-Chloro-6-(dimethylamino)isonicotinic acid (450 mg, 2.24 mmol), 4-(tert-butoxycarbonyl)benzene boronic acid (648 mg, 2.92 mmol), 1,4-dioxane (7.5 mL) and sodium carbonate (713 mg, 6.73 mmol) dissolved in water (3.36 mL) were placed in a flask and the mixture bubbled with nitrogen while stirring for 10 min. Palladium(II) acetate (20 mg, 0.09 mmol) and 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (75 mg, 0.18 mmol) were then added together and the vessel flushed with nitrogen, sealed, and heated at 90° C. for 5 h. The mixture was then cooled to room temperature, diluted with ethyl acetate (50 mL), acidified to pH 2 with 1.5 N HCl and filtered through a pad of celite. The layers were separated and the aqueous portion extracted with ethyl acetate (2×50 mL). The combined organic portions were treated with anhydrous sodium sulfate and decolorizing charcoal and stirred for 30 min before filtering. The solution was concentrated to dryness and the residue purified by trituration with a mixture of methyl tert-butyl ether (5 mL) and heptane (100 mL). The solids were collected by filtration and dried to give 2-(4-(tert-butoxycarbonyl)phenyl)-6-(dimethylamino)isonicotinic acid (502 mg, 65%) as a pale yellow powder. m/z: 343+ [M+H]; 341− [M−H]; 1H NMR (400 MHz, CDCl3) δ ppm 8.12-8.21 (m, 2H), 8.04-8.11 (m, 2H), 7.67 (s, 1H), 7.16 (s, 1H), 3.23 (s, 6H), 1.64 (s, 9H).

Workup

  1. customwere placed in a flask
  2. customthe mixture bubbled with nitrogen
  3. customthe vessel flushed with nitrogen
  4. customsealed
  5. temperatureThe mixture was then cooled to room temperature
  6. additiondiluted with ethyl acetate (50 mL)
  7. filtrationfiltered through a pad of celite
  8. customThe layers were separated
  9. extractionthe aqueous portion extracted with ethyl acetate (2×50 mL)
  10. additionThe combined organic portions were treated with anhydrous sodium sulfate
  11. stirringstirred for 30 min
  12. filtrationbefore filtering
  13. concentrationThe solution was concentrated to dryness
  14. customthe residue purified by trituration with a mixture of methyl tert-butyl ether (5 mL) and heptane (100 mL)
  15. filtrationThe solids were collected by filtration
  16. customdried

Sources & evidence

ORD record
ord-4df317e996a9400eb1ae4a3afd2cc848
Source dataset
uspto-grants-2014_10
Patent number
US08859577B2

Reaction notes

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