Reaction #674319

Reaction equation

compound

tert-butyl (R)-2-(hydroxymethyl)pyrrolidine-1-carboxylate

phenol

triphenylphosphine

diisopropyl azodicarboxylate

→

tert-butyl (R)-2-(phenoxymethyl)pyrrolidine-1-carboxylate

Solvents

DCM

toluene

ether

Conditions

Workup

1. 1
   Extractionthe solution was extracted with aqueous 3N NaOH
2. 2
   WashThe organic layer was washed with brine
3. 3
   Dryingdried over MgSO4
4. 4
   Concentrationconcentrated in vacuo

Procedure

To an ice-cold solution of the compound from Step 1 (2.60 g, 12.9 mmol), phenol (3.64 g, 38.7 mmol), and triphenylphosphine (6.77 g, 25.8 mmol) in DCM (50 mL) was added a solution of diisopropyl azodicarboxylate (5.22 g, 25.8 mmol) in toluene (30 mL). After stirring at room temperature for 60 hours it was diluted with ether and the solution was extracted with aqueous 3N NaOH. The organic layer was washed with brine, dried over MgSO4, and concentrated in vacuo. The intermediate tert-butyl (R)-2-(phenoxymethyl)pyrrolidine-1-carboxylate was obtained from the residue by column chromatography (silica gel, cHex/EtOAc 29:1); yield: 1.82 g (51%).

Source