Cesium carbonate → 2-Chloro-6-(methylpropylamino)-isonicotinic acid methyl ester

HRID 732461Notes

Reaction equation

HRID 732461 reaction equation
[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[C:8]([Cl:10])[N:7]=[C:6](Cl)[CH:5]=1.[CH3:13][NH:14][CH2:15][CH2:16][CH3:17].C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:5]=[C:6]([N:14]([CH3:13])[CH2:15][CH2:16][CH3:17])[N:7]=[C:8]([Cl:10])[CH:9]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 12315N-MethylpropylamineHCID 93237Methyl 2,6-dichloroisonicotinateHCID 634876Binap, (A+-)-

Product 1

HCID 866150102-Chloro-6-(methylpropylamino)-isonicotinic acid methyl esterYield 14.2%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

Mix 2,6-dichloro-isonicotinic acid methyl ester (5 g, 24.2 mmol), methylpropyl-amine (3.2 g, 23.06 mmol), cesium carbonate (10 g, 31.2 mmol), racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (1.5 g, 2.43 mmol), and palladium acetate (0.27 g, 1.21 mmol) in toluene (50 mL). Degas with argon, seal the vessel and heat at 80° C. for 16 h. Cool to room temperature and dilute with diethyl ether (50 mL). Filter through a filtering agent, concentrate, and purify (silica gel chromatography, eluting with 0:100 to 20:80 ethyl acetate:hexanes to give the title compound as an oil (795 mg, 13.5%).

Workup

  1. customDegas with argon
  2. customseal the vessel
  3. temperatureCool to room temperature
  4. additiondilute with diethyl ether (50 mL)
  5. filtrationFilter through a filtering agent
  6. concentrationconcentrate
  7. custompurify (silica gel chromatography
  8. washeluting with 0:100 to 20:80 ethyl acetate

Sources & evidence

ORD record
ord-03ebed38966948a0b4fb8a8efd465a8b
Source dataset
uspto-grants-2009_09
Patent number
US07585885B2

Reaction notes

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