4-Methyl-2-oxovaleric acid → HCID 14303083, compound

HRID 745620

Reaction equation

HRID 745620 reaction equation
[CH3:1][CH:2]([CH3:9])[CH2:3][C:4](=[O:8])[C:5]([OH:7])=O.C(Cl)(=O)C(Cl)=O.[CH3:16][NH:17][C:18](=[O:30])[C@H:19]([CH2:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=1)[NH2:20].C(N(CC)CC)C>ClCCl.O.CN(C)C=O>[CH3:16][NH:17][C:18](=[O:30])[C@H:19]([CH2:21][C:22]1[CH:23]=[CH:24][C:25]([O:28][CH3:29])=[CH:26][CH:27]=1)[NH:20][C:5](=[O:7])[C:4](=[O:8])[CH2:3][CH:2]([CH3:1])[CH3:9]

Participants

8

Reactant 4

HCID 704-Methyl-2-oxovaleric acidHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 14303038O-methyl-L-tyrosine N-Methylamide

Product 1

HCID 14303083HCID 14303083, compoundYield 72.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

4-Methyl-2-oxopentanoic acid (31.3 g., 0.24 mol.) was dissolved in dry dichloromethane (50 mls.) and the resultant solution was cooled to 0° C. To the solution was added dropwise oxalyl chloride (23.2 mls., 0.265 mol.), followed by dimethylformamide (0.5 ml.). The resultant mixture was stirred at 0° C. for 1 hour, and then heated under reflux for 5 minutes and then allowed to cool. O-Methyl-L-tyrosine N-Methylamide (50.0 g., 0.24 mol.) and triethylamine (37.1 mls., 0.265 mol.) were dissolved in dichloromethane (120 mls.) and the resultant solution added dropwise to the cooled reaction mixture. The mixture was allowed to warm to room temperature and stirred overnight. The mixture was poured into water (50 mls.) and the organic layer was removed. The aqueous layer was extracted with dichloromethane (30 mls.), the combined extracts were dried over anhydrous sodium sulfate and the solvent removed by evaporation in vacuo to yield a crude product as a yellow solid (85.1 g.). The crude product was recrystallized from tertiary butyl ethyl ether to yield N-(4-methyl-2-oxopentanoyl)-O-methyl-L-tyrosine N-methylamide (55.6 g.)

Workup

  1. temperatureheated
  2. temperatureunder reflux for 5 minutes
  3. temperatureto cool
  4. customthe organic layer was removed
  5. extractionThe aqueous layer was extracted with dichloromethane (30 mls.)
  6. dry with materialthe combined extracts were dried over anhydrous sodium sulfate
  7. customthe solvent removed by evaporation in vacuo
  8. customto yield a crude product as a yellow solid (85.1 g.)
  9. customThe crude product was recrystallized from tertiary butyl ethyl ether

Sources & evidence

ORD record
ord-1f725cf520964bd6aca9cf2131cdfefd
Source dataset
uspto-grants-1986_07
Patent number
US04599361

Linked notes

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