Methyl L-phenylalaninate hydrochloride → N-(3-methyl-2(S)-(t-butoxycarbonylamino)-but-1-yl)phenylalanine methyl ester

HRID 1900629Notes

Reaction equation

HRID 1900629 reaction equation
C([BH3-])#N.[Na+].[C:5]([O:9][C:10]([NH:12][C@@H:13]([CH:16]([CH3:18])[CH3:17])[CH:14]=O)=[O:11])([CH3:8])([CH3:7])[CH3:6].Cl.[CH3:20][O:21][C:22](=[O:32])[C@H:23]([CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[NH2:24]>CO.C(O)(=O)C>[CH3:20][O:21][C:22](=[O:32])[C@H:23]([CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[NH:24][CH2:14][C@@H:13]([NH:12][C:10]([O:9][C:5]([CH3:8])([CH3:7])[CH3:6])=[O:11])[CH:16]([CH3:18])[CH3:17]

Participants

6

Reactant 3

HCID 75736Methyl L-phenylalaninate hydrochlorideHCID 5003444Sodium cyanoborohydrideHCID 6917569(S)-tert-Butyl (3-methyl-1-oxobutan-2-yl)carbamate

Product 1

HCID 22846564N-(3-methyl-2(S)-(t-butoxycarbonylamino)-but-1-yl)phenylalanine methyl esterYield 82.3%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Procedure

Sodium cyanoborohydride (2.0 g, 0.03 mole) was added portionwise (one hour) to a solution of the known compound 2(S)-t-butoxycarbonylamino-3-methylbutyraldehyde (5.8 g, 0.029 mole) and phenylalanine methyl ester hydrochloride (6.1 g, 0.028 mole) in methanol (150 ml) and acetic acid (1.5 ml). The clear reaction mixture was stirred at room temperature under argon for 2 hours and concentrated in vacuo. The residue was cooled in an ice bath, neutralized with saturated NaHCO3 and extracted (3×) with ethyl acetate. The organic phase was dried (Na2SO4), filtered and evaporated to give a pale yellow residue, which was purified by column chromatography on silica gel using 20% ethyl acetate-hexane. The title compound (8.4 g) was obtained as a pale yellow oil.

Workup

  1. concentrationconcentrated in vacuo
  2. temperatureThe residue was cooled in an ice bath
  3. extractionextracted (3×) with ethyl acetate
  4. dry with materialThe organic phase was dried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated
  7. customto give a pale yellow residue, which
  8. customwas purified by column chromatography on silica gel using 20% ethyl acetate-hexane

Sources & evidence

ORD record
ord-91f1999df70c4dfd93d869ba212c5130
Source dataset
uspto-grants-1996_11
Patent number
US05576293

Reaction notes

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