Methyl iodide → HCID 59423795, compound

HRID 501667Notes

Reaction equation

HRID 501667 reaction equation
[H-].[Na+].[CH3:3][C@@H:4]([CH2:15][CH2:16][CH2:17][CH3:18])[C:5]([NH:7][C@@H:8]([CH2:12][CH:13]=[CH2:14])[C:9]([OH:11])=[O:10])=[O:6].I[CH3:20]>C1COCC1>[CH3:20][N:7]([C@@H:8]([CH2:12][CH:13]=[CH2:14])[C:9]([OH:11])=[O:10])[C:5](=[O:6])[C@H:4]([CH3:3])[CH2:15][CH2:16][CH2:17][CH3:18]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 86622308HCID 86622308, compound

Product 1

HCID 59423795HCID 59423795, compoundYield 80%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Step D (3): General procedure: Sodium hydride (60% dispersion in mineral oil, 231 mg, 5.79 mmol) was carefully added portionwise to a solution of (S)-2-((S)-2-methylhexanamido)pent-4-enoic acid (diastereomer A from Step D (2), 440 mg, 1.93 mmol) and iodomethane (961 μL, 15.4 mmol) in THF (25 mL) at 0° C. The resulting mixture was allowed to warm to rt and stirred overnight (18 h). The reaction was chilled to 0° C. and quenched with EtOAc. The mixture was diluted with water and poured into 1 N NaOH. The aqueous layer was extracted with diethyl ether. The aqueous layer was then acidified with 1 N HCl and extracted with EtOAc. The second organic extract was sequentially washed with aqueous sodium bisulfite solution and brine solution. The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo to provide 370 mg (80% yield) of the title compound (diastereomer A) as a clear viscous oil. Diastereomer B from Step D (2) was subject to the same procedure to afford 580 mg (97% yield) of the title compound (diastereomer B) as a clear viscous oil. Data for diastereomer A: LRMS (M−H)−=240.1 1H NMR (500 MHz, CDCl3) δ ppm 0.82-0.90 (m, 3H) 1.05-1.13 (m, 3H) 1.17-1.42 (m, 5H) 1.62-1.73 (m, 1H) 2.52-2.61 (m, 1H) 2.63-2.87 (m, 2H) 2.99 (d, J=3.36 Hz, 3H) 5.00-5.16 (m, 3H) 5.64-5.76 (m, 1H). Data for diastereomer B: LRMS (M−H)−=240.2; 1H NMR (500 MHz, CDCl3) δ ppm 0.82-0.90 (m, 3H) 1.10 (dd, J=11.29, 6.71 Hz, 3H) 1.17-1.43 (m, 5H) 1.60-1.75 (m, 1H) 2.52-2.83 (m, 3H) 2.99 (d, J=3.05 Hz, 3H) 5.01-5.16 (m, 3H) 5.63-5.77 (m, 1H).

Workup

  1. temperatureThe reaction was chilled to 0° C.
  2. customquenched with EtOAc
  3. additionThe mixture was diluted with water
  4. additionpoured into 1 N NaOH
  5. extractionThe aqueous layer was extracted with diethyl ether
  6. extractionextracted with EtOAc
  7. extractionThe second organic extract
  8. washwas sequentially washed with aqueous sodium bisulfite solution and brine solution
  9. dry with materialThe organic layer was dried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6e0ef6a7199f466fbed3de9d263ad0d3
Source dataset
uspto-grants-2010_08
Patent number
US07772221B2

Reaction notes

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