Cesium carbonate → (S)-2-sec-Butylamino-6-(1,1-difluoroethyl)-isonicotinic acid methyl ester

HRID 732396Notes

Reaction equation

HRID 732396 reaction equation
[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:9]=[C:8]([C:10]([F:13])([F:12])[CH3:11])[N:7]=[C:6](Cl)[CH:5]=1.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.C(=O)([O-])[O-].[Cs+].[Cs+].[C@@H:68]([NH2:72])([CH2:70][CH3:71])[CH3:69]>C1(C)C=CC=CC=1.C(OCC)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:9]=[C:8]([C:10]([F:13])([F:12])[CH3:11])[N:7]=[C:6]([NH:72][C@H:68]([CH2:70][CH3:71])[CH3:69])[CH:5]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 67137532-Butanamine, (S)-HCID 860813552-Chloro-6-(1,1-difluoroethyl)-isonicotinic acid methyl ester

Product 1

HCID 68814766(S)-2-sec-Butylamino-6-(1,1-difluoroethyl)-isonicotinic acid methyl esterYield 86%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Procedure

Dissolve 2-chloro-6-(1,1-difluoroethyl)-isonicotinic acid methyl ester (200 mg, 0.85 mmol), palladium (II) acetate (20.0 mg, 0.09 mmol), racemic 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (56 mg, 0.09 mmol) and cesium carbonate (414 mg, 1.27 mmol) in toluene (3 mL) in a previously degassed sealed vessel. Flush the mixture with nitrogen gas. Add (S)-(+)-sec-butylamine (0.10 mL, 1.02 mmol) to the solution under nitrogen and heat the sealed mixture overnight at 100° C. Cool the reaction to room temperature. Dilute with diethyl ether and filter through a filtering agent. Concentrate the filtrate and purify (silica gel chromatography, eluting with 0:100 to 5:95 ethyl acetate:hexanes) to give the title compound as an oil (86%).

Workup

  1. customa previously degassed
  2. customsealed vessel
  3. customFlush the mixture with nitrogen gas
  4. temperatureCool
  5. customthe reaction to room temperature
  6. filtrationfilter through a filtering agent
  7. concentrationConcentrate the filtrate
  8. custompurify
  9. wash(silica gel chromatography, eluting with 0:100 to 5:95 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-503a92a17af3466d84fc428988e5c8bf
Source dataset
uspto-grants-2009_09
Patent number
US07585885B2

Reaction notes

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