Water → 221298-62-0

HRID 1741256Notes

Reaction equation

HRID 1741256 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([C:12]([O:14]C)=[O:13])[C:5]([C:8](OC)=O)=[N:6][CH:7]=1.[NH2:16][C@:17]([CH3:24])([CH:21]([CH3:23])[CH3:22])[C:18]([NH2:20])=[O:19].CC([O-])(C)C.[K+].O>C1(C)C=CC=CC=1>[CH:21]([C@:17]1([CH3:24])[C:18](=[O:19])[NH:20][C:8]([C:5]2[N:6]=[CH:7][C:2]([CH3:1])=[CH:3][C:4]=2[C:12]([OH:14])=[O:13])=[N:16]1)([CH3:23])[CH3:22]

Participants

6

Reactant 4

HCID 962WaterHCID 11007933HCID 11007933, compoundHCID 117458692,3-Pyridinedicarboxylic acid, 5-methyl-, 2,3-dimethyl esterHCID 23665647Potassium tert-butoxide2×

Product 1

HCID 11471352221298-62-0Yield 68.6%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A stirred mixture of dimethyl 5-methylpyridine-2,3-dicarboxylate (52.25 g, 0.25 mol) and (R)2-amino-2,3-dimethylbutyramide (33.43 g, 0.2563 mol, 96.2% R isomer) in dry toluene is treated with KOt-Bu (29.4 g, 0.2625 mol) at 35° C., stirred at ambient temperatures for 10 minutes, treated with a second portion of KOt-Bu (29.4 g, 0.2625 mol) at 40° C., heated at 80°-85° C. for 1.5-2.0 hr, cooled to room temperature, treated with water and stirred until dissolution of solids is complete. The phases are separated. The aqueous phase is acidified to pH 3 with concentrated HCl, stirred at pH 3 for 10-15 min., and filtered. The aqueous filtrate is extracted with methylene chloride. The filtercake is dispersed in methylene chloride and the dispersion is filtered. The methylene chloride extracts and the methylene chloride filtrate are combined, dried over MgSO4 and concentrated to dryness in vacuo to give the title product as a white solid, 47.3 g, 68.6% yield, 98.1% pure, 97% R isomer by quantitative NMR analysis.

Workup

  1. temperatureheated at 80°-85° C. for 1.5-2.0 hr
  2. stirringstirred until dissolution of solids
  3. customThe phases are separated
  4. stirringstirred at pH 3 for 10-15 min.
  5. filtrationfiltered
  6. extractionThe aqueous filtrate is extracted with methylene chloride
  7. additionThe filtercake is dispersed in methylene chloride
  8. filtrationthe dispersion is filtered
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated to dryness in vacuo

Sources & evidence

ORD record
ord-5601706a07124fc0bfc3aa5956a95115
Source dataset
uspto-grants-1999_10
Patent number
US05973154

Reaction notes

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