Hydrochloric Acid → t-butoxycarbonylmethyl 5-(Boc-amino)-4-oxopentanoate

HRID 1771022Notes

Reaction equation

HRID 1771022 reaction equation
C(N(CC)CC)C.[C:8]([NH:15][CH2:16][C:17](=[O:23])[CH2:18][CH2:19][C:20]([OH:22])=[O:21])([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9].Br[CH2:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27].Cl>C(OCC)(=O)C>[C:8]([NH:15][CH2:16][C:17](=[O:23])[CH2:18][CH2:19][C:20]([O:22][CH2:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])=[O:21])([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 79177tert-Butyl bromoacetateHCID 179898205-((tert-Butoxycarbonyl)amino)-4-oxopentanoic acid

Product 1

HCID 90034544t-butoxycarbonylmethyl 5-(Boc-amino)-4-oxopentanoateYield 89%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Triethylamine (2.22 g; 22.0 mmol) was added dropwise to a stirred solution of 5-(Boc-amino)-4-oxopentanoic acid (4.62 g; 20.0 mmol) and t-butyl bromoacetate (4.30 g; 22.0 mmol) in ethyl acetate (60 mL) under argon at ambient temperature. The mixture (slurry) was refluxed for 17 h, then cooled to ambient temperature, poured into 0.5 M HCl (100 mL) and shaken thoroughly. The aqueous portion was extracted with ethyl acetate (2×20 mL). The combined organic solutions were washed with saturated NaHCO3 solution (1×20 mL) and saturated NaCl solution (1×20 mL) then dried (MgSO4), filtered and evaporated. Evaporation resulted in an amber oil that was purified by flash chromatography on a 40×55-mm silica gel 60 column eluted with ethyl acetate-hexane (1:1) (600 mL), collecting 5×100 mL fractions. Evaporation of fractions 1 and 2 resulted in 6.15 g (89%) product (yellow oil).

Workup

  1. temperatureThe mixture (slurry) was refluxed for 17 h
  2. extractionThe aqueous portion was extracted with ethyl acetate (2×20 mL)
  3. washThe combined organic solutions were washed with saturated NaHCO3 solution (1×20 mL) and saturated NaCl solution (1×20 mL)
  4. dry with materialthen dried (MgSO4)
  5. filtrationfiltered
  6. customevaporated
  7. customEvaporation
  8. customresulted in an amber oil that
  9. customwas purified by flash chromatography on a 40×55-mm silica gel 60 column
  10. washeluted with ethyl acetate-hexane (1:1) (600 mL)
  11. customcollecting 5×100 mL fractions
  12. customEvaporation of fractions 1 and 2

Sources & evidence

ORD record
ord-043ee78e928c4da7b67a8a64d9a49c80
Source dataset
uspto-grants-2016_02
Patent number
US09249086B2

Reaction notes

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