Diisopropylethylamine → N-tert-butyl acetyl-(S)-leucine methyl ester

HRID 54931Notes

Reaction equation

HRID 54931 reaction equation
C(O[C:5]([CH3:9])([CH3:8])[CH2:6]Br)(=O)C.Cl.[CH3:11][O:12][C:13](=[O:20])[C@H:14]([CH2:16][CH:17]([CH3:19])[CH3:18])[NH2:15].C(N(C(C)C)CC)(C)C.CCCCCC.[C:36](OCC)(=[O:38])[CH3:37]>C(#N)C>[CH3:11][O:12][C:13](=[O:20])[C@H:14]([CH2:16][CH:17]([CH3:19])[CH3:18])[N:15]([C:36](=[O:38])[CH3:37])[C:5]([CH3:9])([CH3:8])[CH3:6]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2723695Leucine methyl ester hydrochlorideHCID 197628551-Bromo-2-methylpropan-2-yl acetateHCID 21226206Ethyl acetate hexane

Product 1

HCID 22872264N-tert-butyl acetyl-(S)-leucine methyl ester

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

A solution of bromo-tert-butyl acetate (44.4 mL, 0.275 mol), (S)-leucine methyl ester hydrochloride (50 g, 0.275 mol) and diisopropylethyl amine (191 mL, 1.1 mol) in acetonitrile (400 mL) was stirred at room temperature for 16 hrs and heated at 60° C. for 4 hrs. After completion of the reaction (TLC, hexane-ethyl acetate, 9:1) a small aliquot (5 mL) was taken out and acetonitrile was removed under reduced pressure. Ethyl acetate (100 mL) was added and the solution was washed with water (2×100 mL), 10% aqueous citric acid (100 mL) and water (100 mL). The ethyl acetate extract was dried over sodium sulfate, evaporated under reduced pressure and chromatographed over silica gel column. Elution with 5% ethyl acetate in hexane gave pure N-tert-butyl acetyl-(S)-leucine methyl ester (2) as an oil, [α]D25 -17.2 (c, 2.9, MeOH); 1H NMR (CDCl3): 0.88 (3H, d, J=6.6 Hz), 0.89 (3H, d, J=6.6 Hz), 1.42 (9H, s), 1.48 (2H, m), 1.70 (1H, apparent hept, J=6.6 Hz), 3.24 (2H, ABq, J=18 Hz), 3.29 (1H, t, J=7.2 Hz), 3.68 (3H, s); 13C NMR (CDCl3): 22.34 (CH3), 22.65 (CH3), 24.81 (CH), 28.06 (C(CH3)3), 42.44 (CH2), 49.86 (CH2), 51.74 (OCH3), 59.22 (CH), 81.26 (C), 170.87 (CO), 175.43 (CO).

Workup

  1. customacetonitrile was removed under reduced pressure
  2. additionEthyl acetate (100 mL) was added
  3. washthe solution was washed with water (2×100 mL), 10% aqueous citric acid (100 mL) and water (100 mL)
  4. extractionThe ethyl acetate extract
  5. dry with materialwas dried over sodium sulfate
  6. customevaporated under reduced pressure
  7. customchromatographed over silica gel column
  8. washElution with 5% ethyl acetate in hexane

Sources & evidence

ORD record
ord-82b20cb5c509462ebf9fbc28ab943c75
Source dataset
uspto-grants-1997_04
Patent number
US05624928

Reaction notes

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