Methyl iodide → 1-(tert-Butyl) 2-methyl (2S,4R)-4-hydroxy-2-methylpyrrolidine-1,2-dicarboxylate

Temperatur

-30 °C

To a solution of (2S,4R)-4-hydroxy-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (500 mg, 2.04 mmol) and MeI (1.2 g, 8.45 mmol) in tetrahydrofuran at −40° C. was added a solution of lithium diisopropylamide in tetrahydrofuran (1.5M solution, 5 mL, 7.47 mmol). The reaction mixture was warmed to room temp. and stirred for 4 h. After completion of reaction, the mixture was re-cooled to −30° C. and quenched with saturated aqueous ammonium chloride. The reaction mixture was then extracted with ethyl acetate and washed with water and brine. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The crude was purified by preparative HPLC to give two stereoisomers; (2S,4R)-4-hydroxy-2-methyl-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (200 mg, 37.7% yield) and (2R,4R)-4-hydroxy-2-methyl-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (100 mg, 18.9% yield). MS calcd. for C12H22NO5 [(M+H)+] 260, obsd. 260.

1. temperatureThe reaction mixture was warmed to room temp.
2. customAfter completion of reaction
3. customquenched with saturated aqueous ammonium chloride
4. extractionThe reaction mixture was then extracted with ethyl acetate
5. washwashed with water and brine
6. dry with materialThe organic layer was dried over anhydrous sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. customThe crude was purified by preparative HPLC
10. customto give two stereoisomers

ORD-Eintrag

ord-7b939eb15d5e43c18e6a521d15448ba8

Quelldatensatz

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09090559B2