Cesium carbonate → (S)-2-sec-Butylamino-6-methoxy-isonicotinic acid ethyl ester

HRID 1436597Notes

Reaction equation

HRID 1436597 reaction equation
[C@@H:1]([NH2:5])([CH2:3][CH3:4])[CH3:2].[CH2:6]([O:8][C:9](=[O:19])[C:10]1[CH:15]=[C:14]([O:16][CH3:17])[N:13]=[C:12](Cl)[CH:11]=1)[CH3:7].C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.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>[CH2:6]([O:8][C:9](=[O:19])[C:10]1[CH:15]=[C:14]([O:16][CH3:17])[N:13]=[C:12]([NH:5][C@H:1]([CH2:3][CH3:4])[CH3:2])[CH:11]=1)[CH3:7]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 67137532-Butanamine, (S)-HCID 13611989Ethyl 2-chloro-6-methoxyisonicotinate

Product 1

HCID 68815378(S)-2-sec-Butylamino-6-methoxy-isonicotinic acid ethyl esterYield 93.3%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 634876Binap, (A+-)-CatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

Add (S)-sec-butyl amine (1.18 mL, 11.8 mmol) to a suspension of 2-chloro-6-methoxy-isonicotinic acid ethyl ester (1.69 g, 7.86 mmol), palladium acetate (0.088 g, 0.4 mmol), racemic 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.250 g, 0.4 mmol), and cesium carbonate (3.8 g, 11.8 mmol) in toluene (20 mL) at room temperature and stir 15 h at 80° C. Cool to room temperature, filter through a filtering agent, concentrate and purify (silica gel chromatography, eluting with 5:95 ethyl acetate:hexanes to give the title compound (1.85 g, 93%).

Workup

  1. temperatureCool to room temperature
  2. filtrationfilter through a filtering agent
  3. concentrationconcentrate
  4. custompurify (silica gel chromatography
  5. washeluting with 5:95 ethyl acetate

Sources & evidence

ORD record
ord-287fdd37eec24e3d833ee4d8dd1efa32
Source dataset
uspto-grants-2009_11
Patent number
US07618978B2

Reaction notes

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