2-Pyridone → (2r)-2-benzyl-n-((1S)-2,2-dimethyl-1-methylcarbamoyl-propyl)-2,4-dihydroxy-butyramide

HRID 1158534Notes

Reaction equation

HRID 1158534 reaction equation
[CH2:1]([C:8]1([OH:14])[CH2:12][CH2:11][O:10][C:9]1=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:15][C@H:16]([C:21]([NH:23][CH3:24])=[O:22])[C:17]([CH3:20])([CH3:19])[CH3:18].N1C=CC=CC1=O>ClCCCl>[CH2:1]([C@:8]([OH:14])([CH2:12][CH2:11][OH:10])[C:9]([NH:15][C@H:16]([C:21](=[O:22])[NH:23][CH3:24])[C:17]([CH3:20])([CH3:19])[CH3:18])=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:1]([C@@:8]([OH:14])([CH2:12][CH2:11][OH:10])[C:9]([NH:15][C@H:16]([C:21](=[O:22])[NH:23][CH3:24])[C:17]([CH3:20])([CH3:19])[CH3:18])=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 88712-PyridoneHCID 445856(2S)-2-Amino-N,3,3-trimethylbutanamideHCID 595115463-Benzyl-3-hydroxy-dihydro-furan-2-one

Product 2

HCID 44818994(2S)-2-Benzyl-N-((1S)-2,2-dimethyl-1-methylcarbamoyl-propyl)-2,4-dihydroxy-butyramideYield 25%HCID 44819351(2r)-2-benzyl-n-((1S)-2,2-dimethyl-1-methylcarbamoyl-propyl)-2,4-dihydroxy-butyramideYield 38%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
80 °C

Procedure

3-Benzyl-3-hydroxy-dihydro-furan-2-one (21c) (0.961 g, 5.00 mmol), H-tLeu-NHMe (1.80 g, 12.5 mmol) and 2-pyridone (0.476 g, 5.0 mmol) was suspended in 10 mL 1,2-dichloroethane in a reaction tube. The vessel was sealed with a screw cap and heated in a metal heating block at 80° C. for 24 h. The solvent was evaporated and the residue was re-dissolved in the least amount of 25% acetonitrile in water and the mixture was purified and the diastereomers separated by column chromatography using RP(C-18)-silica and a manual 10-50% acetonitrile in water gradient (with 0.05% HCOOH). The resulting fractions were analyzed by analytical RP-LC-MS and pure fractions pooled together and the solvent was evaporated to give (2S)-2-Benzyl-N-((1S)-2,2-dimethyl-1-methylcarbamoyl-propyl)-2,4-dihydroxy-butyramide (0.424 g, 25%) and (2R)-2-Benzyl-N-((1S)-2,2-dimethyl-1-methylcarbamoyl-propyl)-2,4-dihydroxy-butyramide (0.631 g, 38%).

Workup

  1. customThe vessel was sealed with a screw
  2. customcap
  3. temperatureheated in a metal
  4. customThe solvent was evaporated
  5. dissolutionthe residue was re-dissolved in the least amount of 25% acetonitrile in water
  6. customthe mixture was purified
  7. customthe diastereomers separated by column chromatography
  8. customthe solvent was evaporated

Sources & evidence

ORD record
ord-f2410fe83f0c45609fd1cbcf3326bf9b
Source dataset
uspto-grants-2010_10
Patent number
US07807677B2

Reaction notes

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