Tert-Butylamine → N-tert-Butyl-2-methylpyridine-3-carboxamide

HRID 1094446Notes

Reaction equation

HRID 1094446 reaction equation
[CH3:1][C:2]1[N:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[C:32]([NH2:36])([CH3:35])([CH3:34])[CH3:33].CCN(C(C)C)C(C)C>C(#N)C.ClCCl>[C:32]([NH:36][C:4](=[O:6])[C:3]1[CH:7]=[CH:8][CH:9]=[N:10][C:2]=1[CH3:1])([CH3:35])([CH3:34])[CH3:33]

Participants

8

Reactant 5

HCID 6385Tert-ButylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 6433732-Methylnicotinic acid

Product 1

HCID 59799806N-tert-Butyl-2-methylpyridine-3-carboxamide

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 6344DichloromethaneSolvent

Procedure

A 12-L, three-neck, round-bottom flask equipped with a mechanical stirrer, a thermocouple, and a nitrogen inlet gas adapter is charged with 2-methyl nicotinic acid (302 g, 2.2 mol), EDCI (464 g, 2.4 mol), HOBt (327.3 g, 2.4 mol, 1.1 equiv) and 4.5 L of anhydrous acetonitrile. The mixture is stirred for 45 minutes at room temperature to dissolve most of the solids and is then cooled to 5° C. using an ice-water bath. A mixture of t-butylamine (242 mL, 2.5 mol) and Hunig's base (402 mL, 2.5 mol) in 500 mL of anhydrous acetonitrile and 500 mL of anhydrous dichloromethane is added slowly over 45 minutes, maintaining the temperature below 10° C. The mixture is stirred for 15 hours at room temperature under nitrogen. The solvent is removed under reduced pressure and the residue is dissolved in ethyl acetate (3.0 L) then washed with saturated ammonium chloride solution (2.0 L). The organic-phase is dried over magnesium sulfate, filtered, and concentrated under reduced pressure. Purification of the resultant crude residue by silica gel flash column chromatography followed by trituration with 5% ethyl acetate/heptane gives the title compound.

Workup

  1. dissolutionto dissolve most of the solids
  2. temperatureis then cooled to 5° C.
  3. additionis added slowly over 45 minutes
  4. temperaturemaintaining the temperature below 10° C
  5. stirringThe mixture is stirred for 15 hours at room temperature under nitrogen
  6. customThe solvent is removed under reduced pressure
  7. dissolutionthe residue is dissolved in ethyl acetate (3.0 L)
  8. washthen washed with saturated ammonium chloride solution (2.0 L)
  9. dry with materialThe organic-phase is dried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customPurification of the resultant crude residue by silica gel flash column chromatography

Sources & evidence

ORD record
ord-5bcb7dfda337492ca9dd4b67985d49c1
Source dataset
uspto-grants-2012_03
Patent number
US08133907B2

Reaction notes

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