Cesium carbonate → 2-Benzyloxy-6-sec-butylamino-isonicotinic acid methyl ester

HRID 1436611Notes

Reaction equation

HRID 1436611 reaction equation
[CH3:1][O:2][C:3](=[O:19])[C:4]1[CH:9]=[C:8](Cl)[N:7]=[C:6]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[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:72]([NH2:76])([CH2:74][CH3:75])[CH3:73]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:1][O:2][C:3](=[O:19])[C:4]1[CH:9]=[C:8]([NH:76][CH:72]([CH2:74][CH3:75])[CH3:73])[N:7]=[C:6]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:5]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 2724537(R)-sec-butylamineHCID 57930944Methyl 2-(benzyloxy)-6-chloroisonicotinate

Product 1

HCID 688149302-Benzyloxy-6-sec-butylamino-isonicotinic acid methyl ester

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
105 °C

Procedure

Degas a sealed tube for 5 min and add a suspension 2-benzyloxy-6-chloro-isonicotinic acid methyl ester (1 g, 3.604 mmol), palladium acetate (100 mg, 0.445 mmol), racemic 2,2′-bis-diphenylphosphanyl-[1,1′]binaphthalenyl (307 mg, 0.493 mmol), cesium carbonate (1.2 g, 3.683 mmol) and (R)-sec-butylamine (0.5 mL, 1.387 mmol) in toluene (14 mL). Heat to 105° C. and stir for 20 h. Cool to room temperature, concentrate and purify (silica gel chromatography, eluting with 3:97 ethyl acetate:hexanes) to give the title compound.

Workup

  1. customDegas a sealed tube for 5 min
  2. temperatureCool to room temperature
  3. concentrationconcentrate
  4. custompurify
  5. wash(silica gel chromatography, eluting with 3:97 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-176028b22ecb4394b549b8962444c732
Source dataset
uspto-grants-2009_11
Patent number
US07618978B2

Reaction notes

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