Dicyclohexylcarbodiimide → 2-(t-butoxycarbonyl)ethyl 5-(Boc-amino)-4-oxopentanoate

HRID 1771030Notes

Reaction equation

HRID 1771030 reaction equation
C1(N=C=NC2CCCCC2)CCCCC1.[C:16]([NH:23][CH2:24][C:25](=[O:31])[CH2:26][CH2:27][C:28]([OH:30])=[O:29])([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17].O[CH2:33][CH2:34][C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36]>ClCCl.CN(C)C1C=CN=CC=1>[C:16]([NH:23][CH2:24][C:25](=[O:31])[CH2:26][CH2:27][C:28]([O:30][CH2:33][CH2:34][C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])=[O:29])([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17]

Participants

6

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 16218743tert-Butyl 3-hydroxypropanoateHCID 179898205-((tert-Butoxycarbonyl)amino)-4-oxopentanoic acid

Product 1

HCID 900345122-(t-butoxycarbonyl)ethyl 5-(Boc-amino)-4-oxopentanoateYield 96%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A solution of N,N′-dicyclohexylcarbodiimide (DCC, 3.34 g; 16.2 mmol) in dry dichloromethane (20 mL) was added using a syringe to a stirred mixture of 5-(Boc-amino)-4-oxopentanoic acid (3.70 g; 16.0 mmol), t-butyl 3-hydroxypropanoate (2.31 g; 15.8 mmol), and 4-dimethylaminopyridine (DMAP, 50 mg) in dichloromethane (40 mL) at ambient temperature under argon. The mild exothermic reaction was moderated with an ice-water bath. After stirring 2 days at ambient temperature, the mixture was suction-filtered on a glass-sinter filter. The residue was washed with dichloromethane (3×20 mL). The combined filtrates were evaporated and the residue was purified by flash chromatography on a 45×55 mm silica gel 60 column eluted with ethyl acetate-hexane (1:1) (500 mL), collecting 7×50 ml fractions. After evaporation of fractions 2-4, 5.45 g (96%) product was obtained (pale yellow oil).

Workup

  1. customThe mild exothermic reaction
  2. customwas moderated with an ice-water bath
  3. filtrationthe mixture was suction-filtered on a glass-sinter
  4. filtrationfilter
  5. washThe residue was washed with dichloromethane (3×20 mL)
  6. customThe combined filtrates were evaporated
  7. customthe residue was purified by flash chromatography on a 45×55 mm silica gel 60 column
  8. washeluted with ethyl acetate-hexane (1:1) (500 mL)
  9. customcollecting 7×50 ml fractions
  10. customAfter evaporation of fractions 2-4

Sources & evidence

ORD record
ord-6af39120f4b44f6cb91ea152ebc729ed
Source dataset
uspto-grants-2016_02
Patent number
US09249086B2

Reaction notes

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