Butyl iodide → Methyl-alpha-butyl-n-(diphenylmethylene)phenylalaninate

HRID 899441Notes

Reaction equation

HRID 899441 reaction equation
[CH3:1][O:2][C:3](=[O:26])[C@H:4]([CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[N:5]=[C:6]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[H-].[Na+].[CH2:29](I)[CH2:30][CH2:31][CH3:32]>CN(C=O)C>[CH3:1][O:2][C:3](=[O:26])[C@:4]([CH2:29][CH2:30][CH2:31][CH3:32])([CH2:19][C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)[N:5]=[C:6]([C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

5

Reactant 3

HCID 10962Butyl iodideHCID 24758Sodium hydrideHCID 11142452Rac-methyl-n-(diphenylmethylene)phenylalaninate

Product 1

HCID 87354237Methyl-alpha-butyl-n-(diphenylmethylene)phenylalaninate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of rac-methyl-N-(diphenylmethylene)phenylalaninate (0.50 g, 1.4 mmol) (for synthesis see: O'Donnell et al, J. Org. Chem. 1982, 47, 2663-2666) in 6 mL DMF at 0° C. was added 95% NaH (0.14 g, 5.6 mmol). After 30 min, butyl iodide was added via syringe to the dark red reaction. After 30 min at 0° C., the reaction was warmed to rt for 14 h, then quenched by the addition of water. The aqueous layer was extracted with EtOAc (2×), the combined organics were washed with brine, dried over Na2SO4, filtered and concentrated. Purification by silica gel chromatography (40 g silica, 0->8% EtOAc/hexanes) afforded methyl-α-butyl-N-(diphenylmethylene)phenylalaninate as a viscous oil. 1H NMR (400 MHz, CDCl3) δ 7.57 (m, 2H), 7.37-7.17 (m, 11H), 7.05-7.03 (m, 2H), 3.36 (d, J=11.5 Hz, 1H), 3.32 (d, J=11.5 Hz, 1H), 3.24 (s, 3H), 1.78 (m, 2H), 1.41 (m, 2H), 1.29-1.24 (m, 2H), 0.89 (t, J=7.2 Hz, 3H). LC/MS M+H=400.

Workup

  1. waitAfter 30 min at 0° C.
  2. customquenched by the addition of water
  3. extractionThe aqueous layer was extracted with EtOAc (2×)
  4. washthe combined organics were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by silica gel chromatography (40 g silica, 0->8% EtOAc/hexanes)

Sources & evidence

ORD record
ord-5f1c49f44bf8408fb3bad167e6b3bed0
Source dataset
uspto-grants-2008_04
Patent number
US07354942B2

Reaction notes

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