Diisopropylethylamine → 2-[2-Benzyloxycarbonylamino-propylamino]-pentanoic acid methyl ester

HRID 1433048Notes

Reaction equation

HRID 1433048 reaction equation
[CH2:1]([O:8][C:9](=[O:15])[NH:10][CH:11]([CH3:14])[CH:12]=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH3:17][O:18][C:19](=[O:25])[C@H:20]([CH2:22][CH2:23][CH3:24])[NH2:21].C(N(C(C)C)CC)(C)C.C([BH3-])#N.[Na+]>CO.C(O)(=O)C.[Cl-].[Cl-].[Zn+2]>[CH3:17][O:18][C:19](=[O:25])[CH:20]([NH:21][CH2:12][CH:11]([NH:10][C:9]([O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:15])[CH3:14])[CH2:22][CH2:23][CH3:24]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 563116Benzyl 1-methyl-2-oxoethylcarbamateHCID 5003444Sodium cyanoborohydrideHCID 14118488methyl (2S)-2-aminopentanoate hydrochloride

Product 1

HCID 690279952-[2-Benzyloxycarbonylamino-propylamino]-pentanoic acid methyl esterYield 38.6%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 3007855ZincchlorideCatalystHCID 887MethanolSolvent

Procedure

To a solution of [1-methyl-2-oxo-ethyl]-carbamic acid benzyl ester (12.3 g, 69 mmol) and norvaline methylester hydrochloride (11.6 g, 69 mmol) in MeOH (300 mL) is added diisopropyl ethyl amine (9.4 g, 73 mmol) and 2 drops of acetic acid. After 10 min., ZnCl2 (9.46 g, 69 mmol) and sodium cyanoborohydride (8.72 g, 14 mmol) is added. The solution is stirred at ambient for 16 h. The solution is then concentrated. The residue is dissolved in EtOAc and 1N KHSO4. The organic layer is washed with 1N KHSO4, H2O, and sat. NaCl. The organic layer is dried over MgSO4, filtered and concentrated. The crude product is purified by column chromatograghy eluting with a gradient of 20% EtOAc/hexane to 40% EtOAc/hexanes. The title compound (8.6 gm, 26.6 mmol) is obtained as a foam. MS (ion spray) m/z 323, (M+H).

Workup

  1. concentrationThe solution is then concentrated
  2. dissolutionThe residue is dissolved in EtOAc
  3. washThe organic layer is washed with 1N KHSO4, H2O, and sat. NaCl
  4. dry with materialThe organic layer is dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product is purified by column chromatograghy
  8. washeluting with a gradient of 20% EtOAc/hexane to 40% EtOAc/hexanes

Sources & evidence

ORD record
ord-aa4a4c2600c048e99a1e0176bd434d07
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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