Diisopropylamine → 1-tert-Butyl 3-methyl 3-fluoropyrrolidine-1,3-dicarboxylate

n-Butyl lithium (2.5M/Hexanes, 3.83 ml; 9.575 mmol) added dropwise to solution of diisopropylamine (1.36 ml; 9.62 mmol) at −78° C. Solution was allowed warm to room temperature and stirred for 30 minutes, then cooled to −78° C. A solution of Pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester (2 g, 8.72 mmol) in THF (10 ml) was added dropwise, warmed to −40° C. for 1 hour, then cooled to −70° C.A solution of N-fluorobenzene-sulfonimide (3.02 g, 9.57 mmol) in THF (15 ml) was added dropwise, stirred at −78° C. for 1 hour, then stirred at room temperature overnight. Precipitated solid was filtered, washed with EtOAc (2×150 ml). Organic layer was washed with 1N HCl (30 ml), brine (100 ml), dried (MgSO4), filtered and solvent evaporated. The residue was chromatographed on silica gel eluting with 10% v/v EtOAc/hexanes yielding product as colorless oil (1.38 g: 64% yield). MS (ESMS, MH 249).

1. temperaturecooled to −78° C
2. temperaturewarmed to −40° C. for 1 hour
3. temperaturecooled to −70° C
4. stirringstirred at −78° C. for 1 hour
5. stirringstirred at room temperature overnight
6. customPrecipitated solid
7. filtrationwas filtered
8. washwashed with EtOAc (2×150 ml)
9. washOrganic layer was washed with 1N HCl (30 ml), brine (100 ml)
10. dry with materialdried (MgSO4)
11. filtrationfiltered
12. customsolvent evaporated
13. customThe residue was chromatographed on silica gel eluting with 10% v/v EtOAc/hexanes yielding product as colorless oil (1.38 g: 64% yield)

ORD record

ord-e5331fb5c1804399b654c1dd450ca831

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08546404B2