Hydrochloric Acid → 1-(benzyloxycarbonyl)ethyl 5-(Cbz-amino)-4-oxopentanoate

HRID 1771026Notes

Reaction equation

HRID 1771026 reaction equation
C(N(CC)CC)C.[C:8]([NH:18][CH2:19][C:20](=[O:26])[CH2:21][CH2:22][C:23]([OH:25])=[O:24])([O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:9].Br[CH:28]([CH3:39])[C:29]([O:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)=[O:30].Cl>C(OCC)(=O)C>[C:8]([NH:18][CH2:19][C:20](=[O:26])[CH2:21][CH2:22][C:23]([O:25][CH:28]([C:29]([O:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)=[O:30])[CH3:39])=[O:24])([O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:9]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 298874Benzyl 2-bromopropanoateHCID 113691045-(((Benzyloxy)carbonyl)amino)-4-oxopentanoic acid

Product 1

HCID 900344831-(benzyloxycarbonyl)ethyl 5-(Cbz-amino)-4-oxopentanoateYield 77%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Triethylamine was added drop-wise to a stirred solution of 5-(Cbz-amino)-4-oxopentanoic acid (4.00 g; 15.0 mmol) and the product of 2a (3.65 g; 15.0 mmol) in ethyl acetate (50 mL). The stirred mixture was refluxed for 2 days under argon. After cooling to ambient temperature, 0.5 M HCl solution (50 mL) was added and the mixture was shaken thoroughly. The aqueous layer was extracted with ethyl acetate (2×20 mL). The combined ethyl acetate solutions were washed with saturated NaHCO3 solution (2×15 mL) and saturated NaCl solution (1×15 mL), then dried (MgSO4). After filtration and evaporation an amber oil was obtained that was purified by flash chromatography on a 60×55 mm silica gel 60 column eluted with ethyl acetate-hexane (1:1) (1000 mL), collecting 8×100 mL fractions. Evaporation of fractions 3-5 resulted in 4.92 g (77%) product (oil).

Workup

  1. temperatureThe stirred mixture was refluxed for 2 days under argon
  2. extractionThe aqueous layer was extracted with ethyl acetate (2×20 mL)
  3. washThe combined ethyl acetate solutions were washed with saturated NaHCO3 solution (2×15 mL) and saturated NaCl solution (1×15 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationAfter filtration and evaporation an amber oil
  6. customwas obtained
  7. customthat was purified by flash chromatography on a 60×55 mm silica gel 60 column
  8. washeluted with ethyl acetate-hexane (1:1) (1000 mL)
  9. customcollecting 8×100 mL fractions
  10. customEvaporation of fractions 3-5

Sources & evidence

ORD record
ord-12a7bfa9b09b4052af5c421de5a89922
Source dataset
uspto-grants-2016_02
Patent number
US09249086B2

Reaction notes

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