Triethylamine → N-(2(S)-(t-butoxycarbonylamino)-3(S)-methylpentyl)glycine methyl ester

HRID 259966Notes

Reaction equation

HRID 259966 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:7])[CH2:5][NH2:6].[C:8]([O:12][C:13]([NH:15][C@H:16]([CH:21]=O)[C@H:17]([CH2:19][CH3:20])[CH3:18])=[O:14])([CH3:11])([CH3:10])[CH3:9].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(N(CC)CC)C>ClCCCl.CN(C=O)C>[CH3:2][O:3][C:4](=[O:7])[CH2:5][NH:6][CH2:21][C@@H:16]([NH:15][C:13]([O:12][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:14])[C@@H:17]([CH3:18])[CH2:19][CH3:20]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 122755Glycine methyl ester hydrochlorideHCID 5049666Sodium triacetoxyborohydrideHCID 113902721,1-Dimethylethyl N-((1S,2S)-1-formyl-2-methylbutyl)carbamate

Product 1

HCID 10755806N-(2(S)-(t-butoxycarbonylamino)-3(S)-methylpentyl)glycine methyl ester

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Glycine methyl ester hydrochloride (4.41 g, 0.035 mol) was dissolved in 1,2-dichloroethane (50 mL) and DMF (5 mL) and treated with 3A molecular sieves (10 g) and N-t-butoxycarbonyl-isoleucinal (6.3 g, 0.029 mol) with stirring at 0° C. Sodium triacetoxyborohydride (9.27 g, 0.044 mol) was added, and the pH of the mixture was adjusted to 6 with triethylamine (3 mL, 0.022 mol). After stirring for 18 h the mixture was filtered, concentrated to a small volume and partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc (2×50 mL). The combined organic phase was washed with aqueous saturated NaHCO3 solution, brine, and dried (Na2SO4). Filtration and concentration afforded a residue which was purified by flash chromatography (SiO2, EtOAc:hexane, 1:3) to give the title compound.

Workup

  1. stirringAfter stirring for 18 h the mixture
  2. filtrationwas filtered
  3. concentrationconcentrated to a small volume
  4. custompartitioned between EtOAc and water
  5. extractionThe aqueous layer was extracted with EtOAc (2×50 mL)
  6. washThe combined organic phase was washed with aqueous saturated NaHCO3 solution, brine
  7. dry with materialdried (Na2SO4)
  8. filtrationFiltration and concentration
  9. customafforded a residue which
  10. customwas purified by flash chromatography (SiO2, EtOAc:hexane, 1:3)

Sources & evidence

ORD record
ord-4bbf5c8e1b9c4f328cc777d6459043bb
Source dataset
uspto-grants-1996_06
Patent number
US05523456

Reaction notes

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