Methanol → Methyl(3S,4R)-1-benzyl-4-(2,4-difluorophenyl)pyrrolidine-3-carboxylate

Samarium triflate (6.32 g, 10 mmol) was added to a stirred solution of (4R)-4-benzyl-3-{[(3S,4R)-1-benzyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]carbonyl}-1,3-oxazolidin-2-one, from preparation 29 (63 g, 130 mmol) in methanol (350 mL) at room temperature. The reaction mixture was stirred for 24 hours and the solvent was removed in vacuo. Dichloromethane (290 mL) was added followed by saturated sodium hydrogen carbonate solution (140 mL) and the mixture stirred for 15 minutes. The resulting precipitate was filtered and washed with dichloromethane (250 mL) and water (25 mL). The phases were separated and the aqueous layer was extracted with dichloromethane (2×40 mL). The organic extracts were combined, dried over magnesium sulfate, filtered and concentrated in vacuo to give the crude residue. The residue was suspended in warm cyclohexane (300 mL) and shaken till formation of a solid occurred. The mixture was allowed to stand at room temperature for 24 hours. The solid was filtered and washed with cold cyclohexane (150 mL). The filtrate was concentrated in vacuo to afford the desired compound, 38 g (87%).

1. customthe solvent was removed in vacuo
2. additionDichloromethane (290 mL) was added
3. stirringthe mixture stirred for 15 minutes
4. filtrationThe resulting precipitate was filtered
5. washwashed with dichloromethane (250 mL) and water (25 mL)
6. customThe phases were separated
7. extractionthe aqueous layer was extracted with dichloromethane (2×40 mL)
8. dry with materialdried over magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customto give the crude residue
12. stirringshaken till formation of a solid
13. waitto stand at room temperature for 24 hours
14. filtrationThe solid was filtered
15. washwashed with cold cyclohexane (150 mL)
16. concentrationThe filtrate was concentrated in vacuo

ORD record

ord-feb2092055c849deb82671bf42c730b8

Source dataset

uspto-grants-2010_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07649002B2