Cesium carbonate → (S)-2-sec-Butylamino-6-difluoromethyl-isonicotinic acid methyl ester

HRID 732393Notes

Reaction equation

HRID 732393 reaction equation
[CH3:1][O:2][C:3](=[O:14])[C:4]1[CH:9]=[C:8]([CH:10]([F:12])[F: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:67]([NH2:71])([CH2:69][CH3:70])[CH3:68]>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:14])[C:4]1[CH:9]=[C:8]([CH:10]([F:12])[F:11])[N:7]=[C:6]([NH:71][C@H:67]([CH2:69][CH3:70])[CH3:68])[CH:5]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 67137532-Butanamine, (S)-HCID 860813522-Chloro-6-difluoromethyl-isonicotinic acid methyl ester

Product 1

HCID 68814274(S)-2-sec-Butylamino-6-difluoromethyl-isonicotinic acid methyl esterYield 60%

Reagents, catalysts & solvents 3

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

Procedure

Dissolve 2-chloro-6-difluoromethyl-isonicotinic acid methyl ester (200 mg, 0.9 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 (438 mg, 1.35 mmol) in toluene (3 mL) in a previously degassed sealed vessel. Flush the mixture with nitrogen gas. Add (S)-(+)-sec-butylamine (0.108 mL, 1.08 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 10:90 acetate:hexanes) to give the title compound as an oil (60%).

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 10:90 acetate:hexanes)

Sources & evidence

ORD record
ord-731515a46ce14418a65388ea11b1ab8c
Source dataset
uspto-grants-2009_09
Patent number
US07585885B2

Reaction notes

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