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

Temperature

-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 record

ord-8c85978b1dad47739857d4ab3a17cd77

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09403805B2