Methanol → (S)-2-(3-phenoxy-phenyl)-pyrrolidine

To oven dried round bottom flask is added S,S-EBTHITiF2 (100 mgs, 0.3 mmol) and diluted with THF (5 mL). The flask is sealed and purged with argon. To the yellow solution is added phenylsilane (4.6 mL, 37.5 mmol), pyrrolidine (100 uL, 1.1 mmol), and anhydrous methanol (100 uL, 1.1 mmol). The resulting yellow mixture is stirred for 45 minutes until green color persisted. A solution of 5-(3-phenoxy-phenyl)-3,4-dihydro-2H-pyrrole (1.2 g, 5.05 mmol) in THF (2 mL) is added to the catalyst and the mixture is stirred for 8 hrs. The reaction is carefully quenched with 10% HCl (100 mL) until gas evolution subsided and the pH˜2. The mixture is diluted with EtOAc (100 mL) and the aqueous layer is removed, neutralized with 3M NaOH (50 mL) until basic and extracted with EtOAc (3×100 mL). The organics were combined, dried over Na2SO4, filtered and concentrated under reduced pressures. The solid residue is purified by silica gel column chromatography (100% EtOAc) to give (S)-2-(3-phenoxy-phenyl)-pyrrolidine as a yellow solid (580 mgs, 48%). LCMS m/z 240.1 (M+1).

1. customTo oven dried round bottom flask
2. additionis added
3. addition(100 mgs, 0.3 mmol) and diluted with THF (5 mL)
4. customThe flask is sealed
5. custompurged with argon
6. stirringthe mixture is stirred for 8 hrs
7. customThe reaction is carefully quenched with 10% HCl (100 mL) until gas evolution
8. additionThe mixture is diluted with EtOAc (100 mL)
9. customthe aqueous layer is removed
10. extractionextracted with EtOAc (3×100 mL)
11. dry with materialdried over Na2SO4
12. filtrationfiltered
13. concentrationconcentrated under reduced pressures
14. customThe solid residue is purified by silica gel column chromatography (100% EtOAc)

ORD record

ord-955378c9f9a54c458ec920080a5ab5fc

Source dataset

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08207183B2