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 1 N 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 1 N 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レコード

ord-1fb2c2871c3748ac8a25b1c2910fd612

出典データセット

uspto-grants-2010_10

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07807672B2