Triphenylphosphine → Tert-butyl 3-(pyridin-4-yloxy)azetidine-1-carboxylate

HRID 2171623Notes

Reaction equation

HRID 2171623 reaction equation
[OH:1][CH:2]1[CH2:5][N:4]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:3]1.[N:13]1[CH:18]=[CH:17][C:16](O)=[CH:15][CH:14]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.C1(C)C=CC=CC=1>C1COCC1>[N:13]1[CH:18]=[CH:17][C:16]([O:1][CH:2]2[CH2:3][N:4]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:5]2)=[CH:15][CH:14]=1

Participants

6

Reactant 4

HCID 11776Triphenylphosphine2×HCID 2756801Tert-butyl 3-hydroxyazetidine-1-carboxylateHCID 178418642HCID 178418642, compoundHCID 178459888HCID 178459888, compound2×

Product 1

HCID 24902675Tert-butyl 3-(pyridin-4-yloxy)azetidine-1-carboxylateYield 88.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
55 °C

Procedure

tert-Butyl 3-hydroxyazetidine-1-carboxylate (4.0 g) and pyridin-4-ol (1.8 g) were mixed with THF (50 ml), and triphenylphosphine (6.23 g) was added thereto. A 1.9 M DIAD/toluene solution (12.5 ml) was added dropwise, followed by stirring at 55° C. overnight. Triphenylphosphine (5 g) and a 1.9M DIAD/toluene solution (10 ml) were added to the reaction mixture, followed by stirring at 55° C. overnight. The reaction mixture was concentrated under reduced pressure, and a liquid separation operation was carried out by the addition of EtOAc and 0.5M hydrochloric acid. The aqueous layer was adjusted to a pH of around 10 by the addition of a 4M aqueous NaOH solution, and extracted with CHCl3. The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (CHCl3/MeOH) to obtain tert-butyl 3-(pyridin-4-yloxy)azetidine-1-carboxylate (4.2 g).

Workup

  1. additionwas added
  2. stirringby stirring at 55° C. overnight
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. customa liquid separation operation
  5. additionwas carried out by the addition of EtOAc and 0.5M hydrochloric acid
  6. additionThe aqueous layer was adjusted to a pH of around 10 by the addition of a 4M aqueous NaOH solution
  7. extractionextracted with CHCl3
  8. dry with materialThe organic layer was dried over Na2SO4
  9. concentrationconcentrated under reduced pressure
  10. customThe obtained residue was purified by silica gel column chromatography (CHCl3/MeOH)

Sources & evidence

ORD record
ord-71b19431cd3d416690cd0ae4863cd21e
Source dataset
uspto-grants-2015_06
Patent number
US09051283B2

Reaction notes

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