Triethylamine → Ethyl 4-(3-(2-tert-butylphenoxy)azetidin-1-yl)-4-oxobutanoate

HRID 2041981Notes

Reaction equation

HRID 2041981 reaction equation
[CH2:1]([O:3][C:4](=[O:10])[CH2:5][CH2:6][C:7]([OH:9])=O)[CH3:2].C(Cl)(=O)C(Cl)=O.[C:17]([C:21]1[CH:31]=[CH:30][CH:29]=[CH:28][C:22]=1[O:23][CH:24]1[CH2:27][NH:26][CH2:25]1)([CH3:20])([CH3:19])[CH3:18].C(N(CC)CC)C>C1COCC1.CN(C=O)C>[C:17]([C:21]1[CH:31]=[CH:30][CH:29]=[CH:28][C:22]=1[O:23][CH:24]1[CH2:25][N:26]([C:7](=[O:9])[CH2:6][CH2:5][C:4]([O:3][CH2:1][CH3:2])=[O:10])[CH2:27]1)([CH3:20])([CH3:18])[CH3:19]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 70610Monoethyl succinateHCID 534095303-(2-Tert-butylphenoxy)azetidine

Product 1

HCID 59577031Ethyl 4-(3-(2-tert-butylphenoxy)azetidin-1-yl)-4-oxobutanoateYield 90%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To an ice-cold stirred solution of 4-ethoxy-4-oxobutanoic acid (0.42 g, 2.56 mmol) and DMF (0.03 ml) in THF (15 mL) was added oxalyl chloride (0.35 g, 2.72 mmol). After 1 h the reaction mixture was concentrated under reduced pressure. The resulting residue was dissolved in THF (5.0 mL) and the solution was added to an ice-cold solution of 3-(2-tert-butylphenoxy)azetidine (0.35 g, 1.70 mmol) and triethylamine (0.31 g, 3.06 mmol) in THF (30.0 ml) and the resulting reaction mixture was warmed to room temperature. After 16 h the reaction mixture was filtered, the filtrate 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 4-(3-(2-tert-butylphenoxy)azetidin-1-yl)-4-oxobutanoate (0.51 g, 90%) as a colorless oil.

Workup

  1. concentrationAfter 1 h the reaction mixture was concentrated under reduced pressure
  2. dissolutionThe resulting residue was dissolved in THF (5.0 mL)
  3. customthe resulting reaction mixture
  4. filtrationAfter 16 h the reaction mixture was filtered
  5. customthe filtrate was partitioned between ethyl acetate and water
  6. customseparated
  7. washThe organic layer was washed with 10% sodium bicarbonate, saturated sodium chloride
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by flash column chromatography (silica gel, 50:50 heptane/ethyl acetate)

Sources & evidence

ORD record
ord-390790496e6f4417b2cacc2c97451db5
Source dataset
uspto-grants-2013_11
Patent number
US08586571B2

Reaction notes

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