1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Ethyl 3-(3-(2-tert-butylphenoxy)azetidin-1-yl)-3-oxopropanoate

HRID 2041979Notes

Reaction equation

HRID 2041979 reaction equation
[C:1]([C:5]1[CH:15]=[CH:14][CH:13]=[CH:12][C:6]=1[O:7][CH:8]1[CH2:11][NH:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[C:16]([O:22][CH2:23][CH3:24])(=[O:21])[CH2:17][C:18](O)=[O:19].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>C(Cl)Cl>[C:1]([C:5]1[CH:15]=[CH:14][CH:13]=[CH:12][C:6]=1[O:7][CH:8]1[CH2:9][N:10]([C:18](=[O:19])[CH2:17][C:16]([O:22][CH2:23][CH3:24])=[O:21])[CH2:11]1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 70615Monoethyl malonateHCID 757711-HydroxybenzotriazoleHCID 534095303-(2-Tert-butylphenoxy)azetidine

Product 1

HCID 59577290Ethyl 3-(3-(2-tert-butylphenoxy)azetidin-1-yl)-3-oxopropanoateYield 53.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 3-(2-tert-butylphenoxy)azetidine (0.35 g, 1.70 mmol), ethyl hydrogen malonate (0.25 g, 1.87 mmol) in methylene chloride (20.0 mL) was added EDCI (0.36 g, 1.87 mmol) and HOBt (0.25 g, 1.87 mmol) at room temperature. After 16 h the reaction mixture was concentrated under reduced pressure, the resulting residue was partitioned between ethyl acetate and water and separated. The organic layer was washed with 10% sodium bicarbonate, saturated sodium chloride, dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel, 50:50 heptane/ethyl acetate) to provide ethyl 3-(3-(2-tert-butylphenoxy)azetidin-1-yl)-3-oxopropanoate (0.29 g, 53%) as a colorless oil.

Workup

  1. concentrationAfter 16 h the reaction mixture was concentrated under reduced pressure
  2. customthe resulting residue was partitioned between ethyl acetate and water
  3. customseparated
  4. washThe organic layer was washed with 10% sodium bicarbonate, saturated sodium chloride
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by flash column chromatography (silica gel, 50:50 heptane/ethyl acetate)

Sources & evidence

ORD record
ord-cd9a9ee655f340bd933c08af08c31938
Source dataset
uspto-grants-2013_11
Patent number
US08586571B2

Reaction notes

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