Hydrochloric Acid → HCID 86751008, compound

HRID 263387Notes

Reaction equation

HRID 263387 reaction equation
[CH3:1][Al](C)C.[NH2:5][C@H:6]([C:14]([OH:16])=O)[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C[O:18][C:19](=[O:25])[C@H:20]([CH:22]([CH3:24])[CH3:23])[NH2:21].Cl.[OH-].[Na+]>CCCCCC.C(Cl)Cl.O>[CH3:1][N:21]([C:14](=[O:16])[C@H:6]([CH2:7][C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[NH2:5])[C@H:20]([C:19]([OH:18])=[O:25])[CH:22]([CH3:24])[CH3:23]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 6140L-PhenylalanineHCID 14798Sodium HydroxideHCID 94285Valine methyl esterHCID 16682925Trimethylaluminum

Product 1

HCID 86751008HCID 86751008, compoundYield 34%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolvent3×HCID 8058HexaneSolvent

Procedure

A solution of trimethylaluminum (136.2 mL of a 2M solution in hexane, 272.4 mmol) was added dropwise to a stirring suspension of L-phenylalanine (15.0 g, 90.79 mmol) in 150 mL of methylene chloride at 0° C. (ice-bath). The resultant clear solution was allowed to warm to room temperature and stirred for 23 h. A solution of the free base of L-valine methyl ester (15.22 g, 90.79 mmol) in 100 mL of methylene chloride was added dropwise and the resultant clear solution was stirred at room temperature for 72 h. The reaction mixture was then cooled to 0° C. and with stirring, 6N HCl was dropwise until the pH was 2. The mixture was stirred for an additional 0.5 h followed by addition of 40 mL of 50% aqueous NaOH until the pH was 13. To this mixture was added 800 mL of methylene chloride and 100 mL of water. The organic layer was separated, dried over magnesium sulfate and evaporated under reduced pressure to provide a residue which was chromatographed on silica gel using 5% methanol in methylene chloride as the eluting solvent. The desired fractions were collected and evaporated under reduced pressure to yield 5.0 g (34%) of the title product as a colorless oil. IR (neat, cm-1), C=O (1665.8, 1742.0), N--H (3366.6). 1H NMR and 13C NMR (CDCl3) spectra were both consistent with the title product. Analysis calculated for C15H22ClN2Oe ·1/4H2O: C, 56.41; H, 7.42; N, 8.77; Cl, 11.10; Found: C, 56.34; H, 7.65; N, 8.61; Cl, 10.62.

Workup

  1. stirringthe resultant clear solution was stirred at room temperature for 72 h
  2. temperatureThe reaction mixture was then cooled to 0° C.
  3. stirringwith stirring
  4. stirringThe mixture was stirred for an additional 0.5 h
  5. customThe organic layer was separated
  6. dry with materialdried over magnesium sulfate
  7. customevaporated under reduced pressure
  8. customto provide a residue which
  9. customwas chromatographed on silica gel using 5% methanol in methylene chloride as the eluting solvent
  10. customThe desired fractions were collected
  11. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-08f865fcca944c2fa39a4c1145185d99
Source dataset
uspto-grants-1997_07
Patent number
US05643855

Reaction notes

Loading…